DEPARTMENT OF HEALTH & HUi$AN SERVICES

This letter is in response to the citizen petition that was filed with the Dockets Management
Branch on November 18,1997. FDA has reviewed your petition and has decided to grant the
petition in part and to deny the petition in part.

The Photosciences Network, a FDA-wide, inter-Centergroup of experts on the photosciences,
has reviewed your petition. This evaluation has involved the Center for Devices and
Radiological Health (CDRH), the Center for Drug Evaluation and Research (CDER), and the
Center for Food Safety and Applied Nutrition (CFSAN). A thorough evaluation of the best
scientific knowledge was needed to fully address your concerns. In order to evaluate the public
health consequences of indoor .tanning and the use of tanning products, FDA has cooperated with
other federal agencies, the medical community, and the industry in a series of technical
workshops and scientific symposia. These meetings explored the many areas associated with the
risks fi-om exposure to ultraviolet radiation and the use of tanning products. The first meeting
was a Workshop on “UV, Accessory to Melanoma - If so, How?,” held in Snowbird, UT on July
11, 1998 (Attachment # 1: program of meeting). The second meeting, held at the National
Institute of Standards and Technology (NIST) in Gaithersburg, MD on September l-3, 1998,
was an “International Symposium and Work.shop on Measurements of Optical Radiation
Hazards” (Attachment # 2: program of meeting). A group of experts discussed typical values of
Minimal Erythema Dose (MED) for different skin types at the NIST meeting. The third
Workshop was “Risks and Benefits of Exposure to Ultraviolet Radiation and Tanning”, held at
the Natcher Auditorium, National hrstitutes of Health (NIH) on September 16-18, 1998
(Attachment # 3: program of meeting). These three meetings provided scientific
recommendations from a wide range of government agencies, the medical community, and the
industry.

We will address your requests in the same order as they appeared in the original petition.

1. Petitioner requests that FDA relabel all ultraviolet (UV) tar&g units to recommend stricter
user exposure limits and to warn that exposure to a tanning unit may cause melanoma. Petitioner
also requests that user manuals be required to include the current labeling, especially any
warnings.
97P-0478
Page 2 of 7

FDA notes that user instructions are currently required to include a reproduction of the warning
labels. This requirement appears in the performance standard (21 CFR 1040.20(e)(l)(i)).

FDA agrees that it is possible to acquire more W, particularly WA, from sunlamps than from
solar exposure as shown in work done by FDA scientists (see Attachment #4), if an unlimited
number of sessions are permitted at a tanning parlor. FDA does set recommendations with limits
on the number of tanning sessions at an indoor salon. The FDA performance standard (21 CFR
1040.20(e)( l)(iv)) (Attachment # 5) requires that sunlamp product manufacturers provide a
recommended exposure schedule, and a FDA policy letter dated August 2 1, 1986 (Attachment #
6) provides recommended exposure guidelines, which effectively recommend a limit for the total
daily, weekly, and yearly amounts of ultraviolet radiation. These recommendations may not be
strictly followed by and may not be known to some salon operators or tanners. FDA has
published an Advanced Notice of Proposed Rulemaking (64 FR 6288, February 9,1999) that
solicits comments and information about possible changes to its sunlamp performance standard.
Among the changes FDA is considering are expanding applicability of the ruleto reach certain
individuals who modify sunlamp products, developing new values for recommended doses or
intervals that reflect recent findings concerning WA and WB exposure, and revising labeling
requirements to highlight risks.

2. Petitioner requests that FDA require the warning label “For Indoor Use Only, Not to Be Used
Outdoors,” on tanning products that are not intended to be used outdoors.

FDA denies this request. Labeling of sunscreen drug products and suntanning preparations was
addressed in the rulemaking for OTC sunscreen drug products, published on May 21, 1,999 (64
FR 27666). Labeling requirements for OTC sunscreen drug products are set forth at 21 CFR Part
352, Subpart C. Labeling of sun tanning preparations that do not contain a sunscreen ingredient,
must contain the statement: “Warning-This product does not contain a sunscreen and does not
protect against sunburn. Repeated exposure of unprotected skin while tanning may,increa.se the
risk of skin aging, skin cancer, and other harmful effects to the skin even if you do not burn” in
accordance with the requirements of 2 1 CFR 740.19 FDA believes that these labeling
requirements provide consumers with the necessary information and warnings.

3. Petitioner requests that FDA require all products marketed as “tan accelerators,” “tan
enhancers,” or “tan optimizers” be supported by an approved New Drug Application (NDA).

The FDA denies this request because some of these products may, depending on the particular
circumstances, be regulated as cosmetics that do not require NDAs.

-FDA reviews products marketed to enhance or permit tanning that do not contain a sunscreen
ingredient on a case-by-case basis to determine whether the products are intended solely to
provide a cosmetic benefit (such as moisturizing) or whether they are intended to enhance or
permit tanning by some other mechanism of action (i.e. intended to affect the structure or any
function of the body). (64 FR 27666 at 27669) (Attachment # 7)
97P-0478
Page 3 of 7

4. The petitioner requests that FDA require that all products sold as tanning products be
manufactured and labeled according to the Tentative Final Monograph (TFM). The petitioner
further requests that products labeled “SPF 0” and “SPF 1” be removed from the market.

FDA grants this request in part. .A final monograph completing the TFM except for certain
testing and WA labeling issues was issued on May 2 1, 1999 (64 FR 27666). Products that fall
within the scope of the OTC sunscreen drug product final monograph must comply with its
provisions upon the effective date. These provisions include the requirement that a finished OTC
Sunscreen Drug Product provides a minimum sun protection factor (SPF) of not less than 2. (2 1
CFR 352.10 (64 FR 27666 at 27687)) Such a product providing a minimum SPF of less than 2
would fail to conform to the Final Monograph and therefore be liable to regulatory action. See
‘21 CFR 330.1. A label such as “SPF 0” or SPF 1” on a drug tanning preparation that contains no
sunscreen ingredient would be false and misleading in that it could cause consumers to expect
the product to provide some protection against the adverse effects of the sun when, in fact, it does
not and may cause the product to be misbranded under Section 602 of the Federal Food, Drug,
and Cosmetic Act (the Act) (21 U.S.C. 362) (Attachment # 8) See 58 FR 28194 at 28207.

FDA denies your request to the extent that it requests cosmetic tanning products to meet OTC
drug manufacturing and labeling requirements of the Final Monograph. While the agency
believes that all suntanning preparations should be labeled so that the consumer can use them
safely, the Act does not provide the legal authority for FDA to require that cosmetic tanning
products meet the manufacturing and labeling requirements that apply to products that are OTC
drugs. Cosmetic suntanning preparations are subject to separate labeling requirements set forth
at 21 CFR 740.19. A label such as “SPF 0” or SPF 1” on a cosmetic tanning preparation that
contains no sunscreen ingredient would be false and misleading in that it could cause consumers
to expect the product to provide some protection against the adverse effects of the sun when, in
fact, it does not and may cause the product to be misbranded under. Section 602 of the Act (21
U.S.C. 362).

5. Petitioner requests that FDA not allow ,any oral or vitamin therapy products to claim to
enhance tanning or to treat or prevent W injury without an approved NDA or to remove
products with such claims from the market.

FDA denies your request to “not allow” oral or vitamin therapy products with claims only to
enhance tanning “without .an approved NDA.” Such products could possibly be regulated as
dietary supplements or cosmetics that do not require NDAs.

Ingested vitamin-containing products are dietary supplements if they meet the statutory
requirements in 21 U.S.C. 321(ff). A statement describing the role of a dietary ingredient
intended to affect the structure or function of the body may be permitted to be made for dietary
supplements in accordance with 21 U.S.C. 343(r)(6). Such statements do not make the dietary
supplement for which they are made a drug, for which an NDA would be required.

Oral products with the effect of producing a tanned appearance by deposition of an ingested
ingredient may be regulated as cosmetics. The ingredient that imparts color must be the subject
97P-0478
Page 4 of 7

As noted in our response to number three above, certain products labeled with claims to
“enhance tanning” may be regulated as cosmetics, depending on the intended use of the product,
including product formulation or other label and labeling claims being made for the product.

Tanning products claiming to “prevent W injury” are subject to regulation as drug products (see
64 FR 27666 at 27668). Products claiming to “treat W injury” must be reviewed on a case-by-
case basis to determine whether they are intended to provide a cosmetic benefit or are subject to
regulation as drug products. However, any OTC drug product subject to a final monograph may
not contain a nonmonograph condition (such as a use that has not been determined to be
generally recognized as safe and effective) unless it is the subject of an approved NDA or
abbreviated NDA.

Petitioner requests that FDA not allow tanning products to claim that a product “tans faster,”
“tans darker,” “ optimizes the tan,” .‘.‘enhances the tan” or other category II sunscreen’ drug product
claims on its label, advertising or promotional material.

FDA grants this request to the extent that it refers to tanning products regulated as OTC drugs.
The OTC sunscreen drug product Final Monograph establishes uses that can be included on OTC
sunscreen drug product labeling. These uses do not include the “Category II” claims referenced
in your petition. OTC products falling within the scope of the Final Monographusing the claims
referenced in your petition would be subject to regulatory action. See 21 CFR 330.1.

Advertising and promotion of OTC drug products is regulated by the Federal Trade Commission.
However, the inclusion of promotional statements in the labeling of a drug product is reviewed
by FDA on a case-by-case basis to determine if the statements render the product misbranded
under Section 502 of the Act or an unapproved new drug under section 505 of the Act.
Furthermore, the advertising of OTC drug products subject to a final monograph must prescribe,
recommend, or suggest its use only under the conditions stated in the labeling of the product (21
CFR 330.1(d)).

6. Petitioner requests that FDA carefully review all manufacturers of cosmetic-drug products and
their facilities that manufacture tan accelerators or other indoor tanning products and close those
manufacturers that do not meet acceptable standards.

Manufacturers of drugs and cosmetics continue to be subject to periodic factory inspection in
accordance with Section 704(a)(l) of the Act (21 U.S.C. 374(a)(l))(Attachment # 9).
Furthermore, manufacturers of drug products, including OTC sunscreen products, are required to
comply with current Good Manufacturing Practice under Section 501(a)(2)(B) of the Act ( 21
U.S.C. 35 l(a)(2)(B))(Attachment # 10) and regulations at 21 CFR Part 211 (Attachment # 11).
All drug and cosmetic manufacturers also must assure that their products are properly labeled in
accordance with the requirements of the Act and regulations. FDA intends to continue to pursue
97P-047s
Page 5 of 7

regulatory action against tanning accelerators or other indoor tanning products that do not comply
with the requirements of the applicable laws and regulations as resources permit.

7. Petitioner requests that FDA require each user of a tanning salon be provided with a graphic
warning pamphlet prepared by the American Academy of Dermatology (AAD) and American
Academy of Ophthalmology.

FDA denies this request. In conjunction with other federal and private agencies, FDA has
recently issued such a pamphlet. Over the course of the last few decades, FDA has worked with
the Centers for Disease Control and Prevention (CDC), and others to periodically issue a
pamphlet warning consumers of the dangers of overexposure to ultraviolet radiation. Recently
‘FDA worked with CDC and the AAD to re-issue a revised version of the pamphlet: “The Darker
Side of Tanning” (Attachment # 12). In addition, numerous other pamphlets are available from
the AAD and other organizations. FDA’s performance standard (21 CFR 1040.20(e)) requires
user instructions to include warnings, proper operation of equipment, and “correct exposure time
and schedule for persons according to skin type”.

FDA further recommends that tanning salons use informed consent statements. As with,all
medical procedures and for all medical products, informed consent statements are a valuable part
of delivering needed information to the consumer. In conjunction with the states, FDA has
developed a model standard for regulating tanning salons and has urged the operators of all
tanning salons to incorporate an informed consent statement into their contracts with clients.
FDA has drafted a recommended informed consent statement for use by salon operators. This
model regulation is identified as “Part BB” of the Suggested State Regulations for the Control of
Radiation (Attachment # 13)

FDA denies this request. Although FDA has a range .of authorities.that empower the agency to
regulate tannRng products, FDA has limited authority to regulate the day-to-day operations of
tanning salons. The regulation of individual salons is a state and/or local matter. The
recommended exposure schedules, described in Item 1 above, and developed as a model
regulation for states (Attachment # 13) has served as a model for state and local enforcement.

FDA denies this request. FDA does not have the authority to establish guidelines for
certification of tanning salon operators and workers. State and local government agencies have
authority to establish standards for tanning salon personnel. Model state regulations (Attachment
# 14) have been developed, in cooperation with the FDA, to be used by State and local
authorities in carrying out a regulatory program for commercial sunlamp product users. Some
states have adopted this model regulation, in some cases with modifications.
9713-047s
Page 6 of 7

This model regulation is identified as “Part BB” of the Suggested State Regulations for the
Control of Radiation (Attachment # 13). The latest version contains a requirement for training.
However, the training does not specify that salon operators and workers be required to provide
warnings concerning risk of exposure. The model requires salons to maintain records of training
for salon personnel. The model is available from the Conference of Radiation Control Program
Directors (CRCPD). As the need is identified, this model regulation can be updated, as directed
by the CRCPD Board of Directors.

10. Petitioner requests FDA, with the help of the American Academy of Dermatology, to
examine the list of possible phototoxic drugs and shorten it to a more workable length in order to
provide more useful information to tanners.

FDA denies this request. FDA evaluates the safety of individual drug products. Persons
concerned with photosensitivity effects of particular drug products should consult their health
care practitioner, the product’s package insert, or information sources such as the Physician’s
Desk Reference or MEDLINE. FDA no longer publishes a list of photosensitive drugs. FDA
published this list once in 1990. The list made no distinction between those drugs with rarely
observed and frequently observed photosensitivity events, or the severity of pho tosensitivity
effects. FDA cannot control persons publishing lists of phototoxic drugs based on data gleaned
from the open literature or obtained by FOI requests. Since the W.dose from .tanning beds may
cause greater sensitization than sunlight, it may be unwise to shorten the list of photosensitizing
drugs. With current computer search capability, the length of the list of photosensitizing drugs
should not pose a problem.

StPM-A WORKSHOP I: UV, Accessory to Melanoma - If So, How? 7
Chairs: Jarusz 2. Beer, *Food and Drug Administration, Rockville, Maryland and
Frank de Gruijl, University Hospital, Utrecht, The Netherlands -
.
The purpose of the workshop is to review our knowledge on the relationships between UV exposure and
melanoma induction. This issue will be .addressed at the workshop from perspectives ranging from the
epidemiological to the molecular. Human UV exposure will be also be presented from the viewpdinf of melanoma
induction. The contributors areasked to provide the background information and refer to important published data
in addition to the presentation of their ownwork. Atargeted discussion on two theses will conclude the workshop.

1. UV exposure causes melanoma in humans: the public must be re&larly~med about
particular risks of (a) exposure of children and (b) overexposure
2. UVA plays a dominant role in UV-induced human melanoma .
2.1. Use of (UVB blocking) sunscreens and WVA tanning devices should therefore
be discouraged.
2.2. It would be safer to tan using solar emission sunlamps rather than “UVA”
sunlamps.

This ‘workshop is intended to bring together photobiologists and photochemists who are engaged in
$ teaching at the undergraduate l&et and who involve undergraduate students in their research. Topics’will include
’ the appropriate scope of such courses, exampIes of successful laboratory exercises’and student research projects,
and means of interesting both students and the general public in photobiology and photochemistry. The
workshop ‘will conclude with a period of open discussion.

Co.mmission Xnternatiouale de I’Etilairage
International Commission on Non-Ionizing Radiation Protection
National Institute of Standards and Technology, Optical Technology D.ivision
US Army Center for Health Promotion and Preventive Medicine, Laser/Optical Radiation
Program
Center for Devices and Radiological Health, Food and Drug Administration
hmfttt Synpcsium Program

A workshop focusing on the effects that ultraviolet A and ultraviolet B radiation have on the skin will be
held at the Natcher Conference Center, National Institutes of Health, Bethesda, MarLland. The workshop
will begin at 7 p.m. on Wednesday, September 16, and adjourn at 2:30 p.m. on Friday, September 18,
1998.

The workshop is being cosponsored by:

l National Institutes of Health: the National Institute of Arthritis and Musculoskeletal and Skin
Diseases, the National Cancer Institute; the National Institute of Environmental Health Sciences,
and the National Institute on Aging
l Centers for Disease Control and Prevention: the National Institute for Occupational Safe.ty and
Health and the National Center for Chronic Disease Prevention and Health Promotion
l Food and Drug Administration.

The purpose of the workshop is to review the state of the science regarding ultravioIet A and ultraviolet
B radiation, and to address the health effects of various methods of inducing a tan and using sunscreening
agents. s

This meeting has important public health implications, and recommendations resuhing from it will guide
future research directions in this area.

The workshop.format wit1 c&sist of formal presentations followed by panel discussions, which .will be
open to attendees. At least one-half of the time allotted to each session will be devoted to di&rssion.

The preliminary agenda is posted at Agenda

Attendees should include basic and clinical researchers, members of the medical community, and .
representatives from government, industry, and the public..
..
The registration fee ‘is $150 for non-government re&rants. The f& is waived for Federal Goverment
employees. To retister. nlease acc& the registration form
I

ABSTRACT past several decades among the Caucasian population (1). It
Exposure to solar W raditition is a risk factor for cuta- is well established that solar exposure is a significant risk
neous malignant melanoma (CMM). Epidemiol&ic studies factor in the development of this disease (I-3). Melanoma
have also considered the use of sunlamps as a $ossibIe con- incidence demonstrates an inverse dependence on latitude,
+ibu+&r to CMM. We measured and analyzed the e@ssion though this relationship is not as pronouncfl 2is it i? for ,
spectra of six different currently marketed sunlamps and a nonmelanoma skin cancer (NMSC) (1). T
historical s&amp, the UVB-emitting FS I&I& and com- Several epidemioIogic studies have concluded that exb-
pared the results to solar exposur& -For a typical tanner (20 sure to W radiatidn from sunlamps appears to be a risk
St&o.% @ 2 minimal eryUlema .dases (MED)/session), the factor for melanoma (4-7). An epidemiologic study per-
annual WA doses from commonly used fluoFnt sun- .folmed in Sweden (5) found a significant association (odds
lamps were 0.342 times that recei&d from the sun. For a ratio [OR] = 4.2,95% c&dence interval [Ct] = 1.6-l f.?)
frequent tanner (100 s&ions 8 4 MED/session), the annual for melanomas of the trunk with > 10 sujamp exposures per
WA doses from fluorescent sunlamps were 1.Z4.7 times year. Previous epidemi?logic studi& ,from Cam& and Eu-
that received fi-om the sun and 12 times for r&e&y avail- rope have reported odds ratios in the rr+ge of 1.1-2.9 for
able, high:prez+re sudamps. To detem&e ~biologicaIly ef- individuals who ever used sunlamps versus no use (4.6-S).
fective doses, action spectra fqr squamous cell carcinoma The strength of association tended to increase as sunlamp
@CC) in humans and for melanoma in the X+hophorus
usage increased (4-6). indicating that cumulative, intense
fish (XFM) wee% applied to the sunlamps’ emission spectra.
doses, such as those received from sunlamps, may play a
The results for the ef&tive doses using the SCC a&n
role’ 6 melanoma etiology.
spectrum tracked the UVB dw, while the’ results using
the XFM action spectrum tracked the WA doses. When To tisess the wavelength-dependence of W-induced
combined with W ftxpmre received from the sun, typical melanoma, an action spectrum for induction of melanotia
sunlamp .Use results in an approximate doubling of ,annual (I&sfter referred to as XFM) has been determined in the
eEective dose, if the XFM action spectrum is applied. Fre- ~iphophom.s fish (9). & this action spectruni the WA (320-
quent use, however, can ‘ncrease the annual effectlve XFh% 400 am) waveleng+s are only S-50 times I&s effective than
dose by as much as 6 times what would,be.received from UVB (290-320 .nm) in inducing melanoma. Also, a recent
*e sun aIone for fluorescen tsunIampsandasmuchas12 study using Mmwdelphis domestica, a South American
times for newer, high-pressure sunlamps. opossum, found that WA exposures of 25 kJ/m2 were as
effective as UVB exposures of 250 J/m* (i.e. a factor of 100
difference) in iqiuciug’ precursors of melanoma (10). These
INTRODUCTION restits are significantly different from induction of e+hema
The incidence of cutaneOus malignant melanoma (CMM)? in humans (11) or squamous cell carcinoma (SCC) in miw
has been hicreasing at rates of 4-5% per annum over the (12) where the WA wavelengths are about 1000 times less
effective than the UVB ,wavelengths. .-
*To whom correspondenceshould be addressed at: Elcctro-optics Because the e&ion spectra from most sunlamps is sig-
Branch (HFZ-134). Center for Devices and Radiological I-k&h. r&candy differeht than that from the sun. we examined the
Food and Drug Administration. 9200 Corporate Boulevard, Roclc- differences in UVB and WA outputs from various sun-
ville. MD 20850, USA. Fax: 301-827-4677;
e&ail: SYM@CDRH.FDA.CiOV lamps and compared them with solar exposures. In addition,
tAbbrevialions.- CMM, cutaneous malignant melanoma; FDA, Food the sunlamps’ emission spectra were weighted with two dif-
and Drug Administration; MED. minimal erythema dose; NIST. ferent action spectra to determine the difference in biological
National Institute of Standards and Technology; NMSC. nonme- effectiveness between. kunlamp and solar exposure. Spectral
lanoma skin cancer; SCC. squamous cell carcinoma; UVA. 320-
400 nm: UVB. 290-320 nm; WEAC. Winchester Engineering and irradisnce data were obtained from sunlamps typical of thee
Analytical Cents, XFM. Xiphophorus fish melanoma. sold in the U.S. over the past two decades and from two
CJ1998 American Society for Photobiology0031-8655’98 $5.00+0.00 newly marketed sunbeds. Spectra were also obtained from

63
64 Sharon A. Miller et a/.

the two most commonly sold sunlamps in Sweden to deter-
mine if there W& any significant spectral differences that
might account for the epidenuologic findings from the Swed-
ish study (5). These lamps are likely to be typical of sun-
lamps used in that country for rhc last IO-20 years. The
relative risk from sunlamp exposure versus solar exposure
was determined using both the XFM action spectrum (9) and
the SCC action spectrum (determined in the hairless mouse,
corrected for human skin transmittance) (R2). The SCC ac-
tion spectrum was used because it is more similar to action
spectra for erythema in humans and DNA damage, and’it
was developed for a mammalian model. It has yet to be
shown that the XFM action spectrum is applicable to hu-
mans: Significant modifications may be required to account
Wavelength (nm)
for differences in skin transmittance and possible differences
‘in the underlying processes that lead to melanoma. between
the two species.
A survey ,of sunlamp users in the UK rep&s that the
typical use pattern is 20 visits per .year, but 7%.of patrons
.
use sunlamps 100 times per year or more (13j. Therefore,
the following two patternsof sunlamp eqnxure were con-
sidered ‘in this, evaluation; (1) a typical’usk pattern of 20
sunlamp sessions per year. at 2 minimal erythema.doses
. (MED)/session and (2) a frequent use pattern of 100 su&np,
sessions per year at’4 MED/session.

MATERIALS AND MEfTHODS
UVR sources. Spectral irqdiance measurementsfrom over 100
UVA sunlamps (s*mgle. bare lamps) sold in the US wem performed a00 350 400 4so
.
at the Food and Drug Administration’s (FDA’s) Wiuchester Bngi- Wavehqth~trim) t
meeting -and Analytical Center (WBAC). The spe&a generally fell.
into otie of three categories.matchingthe threedifferentUVA phos: Flguke 1. Spectral ii-radiance versus wavelength for thte+ different
jhors used in sunlamp. manufactute that produce emission spectra phosphor combinations ihat are Lsad in sunlamps. Thi l&u plot A
that peak at approximately. 34fl em. 350 nm or 366 nin as demoa- more readily demonstrates. the’ spectral diffeume between the
strated in Fig. 1A and’B. From these data, two lamps, representing lamps, whepaas the logarithmic plot B allows theoutput in.the UVB
the 340 nm and 366 nm groups, were chosen for this study. In and WC regions to be’tepresentbd also. The absolute output of the
addition, two lamps commonly used in Sweden were also includ6d: lamp with spectrumof type III was scaled upward by a factor of
they were of Europeanmanufactureand wereevaluatedat the Swed-. 2.5 to allow for easier comparison of the three typea of phosphots.
ish Radiation Protection Institute. In th+e figins the lamp output was not corrected with the SpectraI
A total of ,seven tanning devices were evaluated .in this study. In transIniaanee of. any acrylic filter.
the casesin which the output from only a singlebunp wasmeas~ ..
the output was adjusted to simulate the radiation levels received in .. ,_

a typical tanning situation, consisti,ng,of a bank of closely spaced 1.6 mu with a wavelength accuracy of 20.5 nm). The calibration of
sunlampsin a sunbed or tanning booth. Sii eurremly txsedtanning. the Optronies 742 is traceableto the National Instime of, Standards
devices were includedztwo lG0 W WA fluore&ent.lamps selected and Technology (MST) through the Swedkh National Testing and
fi-om lampscommonly usedin sunbedsin the USidentitied aqIamps ResearchInsthute. Bar&The overall uncertainty assoekted with
; i f 1 and 2; two 100 W UVA fluoresoent lamps selected from lamps the measurementomeessis estimatedat 15%. .
I commonly used ht sunbeds in Sweden identified as lamps 3 and.4 The two sunb&ps ‘from Sweden (single bare lamp, no reflector)
? a high-speed sunbed unit consisting of 24-160 W fluorescent lamps were measured at a distance of 1 nun At thii close distance. the
that contain significantly more WB than most WA suniamps ind input aperture of the detector “sees’* an appamntly infinite tield of
4-400 W filtered high-pressure a& lamps in the facial ana; and a radiation. This radiation field is similar to the radiation from a sun-
UVA sunbed consisting of an array of 18-1600 W high-pressmearc bed consisting of a closely spaced bank of lamps in front of a n-
lamps filtered to emit radiation ,primarily at wavelengths longer than elector at a use distance of 2-3 cm. This relationship was verified
330 nm and a historical tanning device: a UVB fluorescent FS lamp by eompasing the output of a single lamp at 1 mm to measurements
(used >20 years ago.for tanning). of the output of the lower half of a sunbed. both measured with a
Spectral irradiaticc data for the sun (including direct and diffuse handheld photometer (Digiphot. United D&ctor. Tc~hnol~gie~.
radiation) equivalent to a clear day, at noon. in July in Washington, Hawthorne, CA). These measurements indicated that the, irradiance
DC (latitude 38.9%. zenith angle of 1Y. 3.2 mm atmospheric from an approximately flat field of radiation (i.e. ‘the lower half of.
ozone) ( 14) was also included in this analysis. for comparison. These the sunbed) does not decrease significantly (5%) with distance
solar itradiance data were generated from an empirical equation de- until the detector distance approaches 25 cm (approximately one-
veloped by Diffey (15) based upon the measurements of Bener (16) thud the smallest dimension of the field).
that were performed over a period of years for different atmospheric The two US sunlamps (single bare lamp. no retleetoi) were mea-
ozone concentrations. sured at a distance of 50 cm with a double-grating spectroradiometer
Measuremenu. The two lamps that were evaluated in Sweden . (Optronics model 747). The input of the spectroradiometer was a
were measured with an Optronics model 742 (Optronics Laborato- 7.6 cm-diameter integrating sphere with a 4 cm2 entrance aperture.
ries. Orlando. FL). This double-grating spectroradiometer has a te- Spectral irradiance was measured at 5 nm intuvaIs (instrument
Aon diffuser input with cosine angular response. The spectral irra- bandwidth was 5 nni, with a wavelength accuracy of 20.2 nm). The
diancc was measured at I nm intervals (instrument bandwidth was spectroradiometer system was calibrated by measuring a 100 W
Photochemistry and Photobiology. 1998, 68(l) 65
:
the &a& of a b&gically relevant exposure, the MED. The SCUPh
action spectrum for human SCC (12) and the XFM actio.n spectrum
,000
for melanoma in Xiphop/tr;rrcr (arithmetically derived through straight-
100 i
line interpolation from data published in Setlow ef af. (9)) were used
to weight doses for cancer effectiveness. The SCC action spectrum
10 -
was derived from a carcinogcnesis action spectrum for hairless mice,
adjusted to account for differences between mouse and human epi-
1 dcrmal transmittance and normalized to one at 299 nm (12). The XFM
action spectrum has not been adjusted to account for differences be-
.f tween XipIropImrns and human skin transmittance or other possible
differences that may exist in the melanoma development process be-
.o, tween the two species. As published. the XFM action spectrum begins
and is normalized to one at 302 nm but has been extrapolated to 295
.oa nm (at a value of one) for the purposes of this analysis.
The spectral irradiance at 5 nm intervals (1 nm for the lamps
.ooo1~
20
measured in Sweden) emitted by each tanning device was weighted
with each of three different action spectra and integrated over the
Wavelength (run)
relevant UV wavelength region to give the effective spectml.itm-
Figure 2. Spectral it-radiance versus wavelength for the FS-type diance. lQ .
UVB sunlamp and for the two sunbeds: the high-pressure WA sun-
bed consisting of 18-1609 W filtered high-pressure lamps and the EC,= 400’K% a (1)
new high-speed sunbed consisting of 24-160 W fluorescem lamps I 295
combined with 4-400 W filtered high-pressure lamps in the facial where & is the spectral itradiance (W/(m* nm]) aad S, is the action
area. The absolute output indicated represents exposure levels under spectrum of interest.
typical use conditions. UVB, WA and effective doses per MED. The integrated itradi-
. ante values were converted to the UVB, WA and effective doses : 9.
that one would.rezeive in the time required to reach 1 MED. The
quartz halogen standard lamp that was calibrated by NIST. Assum- calculated “time to 1 MED” was determined by taking the cry-
ing sunlamp instability .of i: 10%. the total uncertainty (determined themally effective in-adiance for each source and dividing it into a,
as a combination in quadrature of random errors and source insta- standard MBD for a Person with skin type II of 200 J/m* (17): ‘.
bility) is estirnated’at 12.5%. 200 J/m*
The measured spectial itradiance from the single.US lamps was .tkn, = m (2)
adjusted to the.intensity level of an entire sunbed Bt a distance of E&S, dx
2-3 cm, again with the assistance of a handheld photometer. To I 295’.
account for geometrical differences in source size as *‘seen” by the
.detector: au additional uncertainty of an estimated 10% should-be where S, is the CIE erythenral actionspectrum in this calculation. .
added to the previous uticertaiqty value of 12.5%.bringing ‘thetotal The UVB and WA doses received .@erMBD were detetmlned
uncertainty to 16%. by multiplying the UW? and UVA dose rates (W/m2) by the time
The adjusted emission spectraof IamPs 14 ,were weighted with .to 1 MBD (s). The effective doses received per MBD were deter- .
the spectral transmittance of a typical 5 mm-thick acrylic panel com- mined by multiplying the SCC-weighted effective -irradi&es (WI
monly used in sunbeds (dam obtained from Steve Rothenberg at m*) and the XPM-weighted effective irradiauces (W/m*) by the time
Itkterleettic. Warren, PA). This result simulated the spectral intensity to 1 MBD (s). These values were then divided by the analogous
that a sunbed user would receive at a distance of 2-3 cm, from a results from the solar irradiance data, so that all further results ‘are
bed consisting of l&24 closely spaced lamps ‘in front of a reflector, relative, to the sample solar spectrum
behind an acrylic panel.
The UVBlFS lamp, the high-speed sunbed and the high-pressure RESULTS
UVA sunbed measurementswere performed with a portable spec-
tromdiometer system (Optromcs model 752). The spectral outputs . E&&ion spectra .
of these lamps are shown in Pig. 2. .Tbheinput of the spectromdi- The three types of spectra; types I., Ii and III, found. by ex-
ometer was a. 10.2 cm-diameter integrating sphere with a 9.6 cm*
pntrane aperture. Spectral irradiice was measured at 5 nm inter- amining the output of the many sunlamps evaluated ,by
vals (instrument bandwidth was 5 nm, with’s wavelength accuracy WBAC over the past few years are shown -by the three dif-
‘of Z-0.2 nm). The spectroradiometer system was calibrated by mea- ferent lamp output spectra in Fig. LA and B. The two lzunps
suring a 1000 W quartz halogen standard lamp that was calibrated from the US ma&et have emission spectra similar to Iamps
by NIST. Assuming soutce instability of -C10%. the total uncertainty type II and III, while-the two lamps from the Swedish market
(determined as a combination in quadrature of random errors and
source instability) is estimated at 125% for the sunbed measure- have emission spectra similar to lamps type I and IL
ments. The spectral itradiance of the single UVB/PS lamp was mea- The integrated W spectral irradiances (below 320 nm
sured and adjusted to a radiation level equivalent to what one would [UVC plus UVB] and above 320.~1 [UVA]) .for each sun-
receive in an older style UVB lamp-equipped tanning booth by com- lamp and for the sun are presented in Table 1. The output
parison with data from actual tanning booth measurements provided
by Dr. Robert M. Sayre (Rapid Precisiou Testing Laboratories, Cor- Ievels below 295 nm from lamps 14 were insignificant after
dova. TN, personal communication). As before, an additional un- filtration through the acrylic panel. The values in Table 1
certainty of an estimated 10% should be added to the uncertainty demonstrate that all of the currently used sunlamps emit
value of 12.5% to account for geometrical differences, bringing the more UVA radiation than UVB radiation. The proportion of
total uncertainty to 16%. UVA. emitted by lamp 2 (95.7%) was most similar to that
The measurements of both sunbeds were performed with the input
aperture of the integrating sphere centered (facing up) under the top. of the sun (94.7%), whereas the emission spectra of lamps
curved canopy of the bed. To simulate actual exposure conditions, 1. 3 and 4-contained more than 97% UVA radiation.
the integrating sphere was positioned at 20 cm above the lower bed
surface. at approximately the position of a user’s midabdomen, with UVB and UVA dose rates
the upper canopy closed.
Acfion spectra weighfing. The CIE-adopted action spectrum for The UVB dose rate from lamps 14 was ‘0.21-1.34 times
erythema (1 I) was used so that effective doses could be compared on that from noontime summer sun, while the UVA dose rate
66 Sharon A. Miller et a/.

Table 1. Integrated-it-radiance for rhc UVB and the UVA rogion$ f& sbiilamps and the s:jn

was approximately 2-3. times that fmrn the sun. The high- UVB, WA and effective-dos&/MED - ’
speed sunbed emittti approximately 25 times the.WB dose Effective dose rates were normalized to a biological expo- -*
rate and 6 times the WA dose rate of the sun. The high- suie unit, 1 MED.’ and are presented as reIative values to the
pressure WA sunbed &&ted 13 times the WA dose rate ” output from the sun cable 3). The last row in’this table iists
of the sun. . the absolute solar doses from- wliich the .absolute values for
.
the sunlamps can be determined. On a per-MBD basis, the
Effective dose rates WB doses from lamps 14 are 0.48-0.85. times &it of the
sun, while the WA dosesare 1.14.1’times that of the sun..
The effective dose rates for the tanning dei$es and the sun Tine WA dose per MED from the high-pressure UVA sun-
are shown in Table 2. For lamps l-4, there was appioxi- ~bedis1Otlmesthat~ofthesUn.
mateIy a factoi of 3 difference betweeh the least and most ime effective dose at 1 MBD was determined tim both.
effective lam@. in terms of er$he& and SCC-effective dose thi SCC dose rates and the m dose rates. The SCC dose
rate. These two effective dose rates for ksnp~ 14 and the per MBD for all the WA sunlampsand sunbeds was 0.66
sun are .very siniilar, but they are @proximately 3 and 8 0.87 tiauq that of the sun, while for the FS lamp it was
times higher for the high-speed sunbed and the BS .lamp. equal to that of the sun. However, the XFM dose per MED
respectively. The XFM dose rates are 2-4 times higher than of 1aGps 14 and the high-pressure WA sunbed was 1.5
that from the sun in the case ,of lam@ 1-p and 8. and 12 4.5 and 9.8 t&es that of the sun, respectively. The XFM
rimes highei than.that from the sun for the high-speed sun- _dose .&r ‘MED’ for the. BS lamp was only’ 0.02 times that of
bed and the high-pressure WA..sunbed, respectively. . *thesun. .’
Annual dose (MED) from the sun
kable 2. Effective ‘dose rate for qthem& &X and melanoma Next the annual cumulative doses were com@red for both
calculated for the different sunlampsand the sun ‘undertypical use su@mp exposure and solar exp;Osure. This analysis was .
conditions+ based on the annual solar exposure of two types of indoor
workers, typical and. frequent tanners. previous studies have .
shown that typical -mdoor workers receive approximately 2-
source ‘(%Z -(wEftJ @E&f)
4% of the available ambient solar W during nonvacatioa
J-amp 1 (US) 0.08 . 0.13 21 time (18.19). The available annual solar W in the Wash-
Lamp 2 (US) 0.27 0.52 20 ington, DC area has been determined to be approximately
Lamp 3 (Sweden) 0.16 0.22 ” 38’ 3500 MBD (20) ‘lf we choose a median value of 3% of the
Lamp 4 (Sweden) 0.22 0.40 28 total for a typical indoor worker and add an additional 1%
Sunbeds for vacations (21). this translates to a total annual solar dose
High-speed ,. 0.66 I.1 82 of 140 MED. For frequent tanners, the annual solar exposure
High-pressure UVA 0.22 0.33 120 has been found to be up to 10% of the available dose (22).
UVIVFS-type ” I.4 3.2 1.7 This would translate to an annual solar dose of 350 MED in
Solar-noon, July, the Washington, DC.area;
Washington, DC 0.18 0.39 9.7
Annual dose (MED) from sunlamps
*All values, in effective W/m2. represent- the integrated icffcctive This analysis assumes one of two different sunlamp/solar
irradiance from 295 to 49 nm for each action spectrum. exposure patterns: typical and frequent. of 20 and 100 ses-
. .
I”

Photochemistry and Photobiology, 1998, 68(i) 67
_ “#,<I‘s ye!:;L,,
Tabie 3. The UVB-. UVA and effective (SCC and Xi%@ do.& Per h&D froth sunlamps relative to that of the sun

sions per y&u and 140 and 350 MED from the sun pei yea& or a&r 3:00 P.M., their annual solar WA d9k.e could be
respectively. During a tanning session, a patron dan receive _ significantly. higher, as .the propo$on of WA to erythema-
from 0.8 MED (13) to the maximum of 4 MJXD, which is effective’ radiatick is tiuch larger at these times &day. I
specified by the US FDA policy on tier limits (23). We The annual WA doses from the sunlamps and the sun’
assumed an average exposure of 2 MED per session or 40 were calculated based on the annual number of MED for the
MgDiyear fro? 20 sessions for t$e typical ~ertsunlamp two exposure p?tierns and are shown in Table 4:The WA
user. For the fkquent tannerLsunlamp user, we assumed the dose received from 20 sessions. at 2 MED per session and
maximum of 4 MEDkssion or 400 -D/y& 66m 100 during 100 sessioti at 4 MED per session was calcul+d .
sessions. The results iri.Tables 4 and 5 have been based ‘on for each s-p. When compared. to solar expdsure, 20
these twd exposure patterns. v&its to a tanning salon at 2 MED per session cqn contribute
an additional 0.31-1.2 times k individual’s annual solar
AnnuaiUV& do&s WA dose for lamps l-4 and as much as 2.9 times for a
high-pressure WA sunbed. In the case of a frequent tanner,
The annual ayailabIe WA from ‘the stin was estimated to 100 visits to a tanning salon at 4 MED per’ session can con-
be 192 500 W/m* based on 3500 .MJZD/y&r multiplied by 55 tribute 124.7 times an i&ividual”s annual solar dose for
kJ/mz/MED (Table 3). For a typical taqner, with an annual lamps l-4 and as much as 12 times for 100 sessions under
exposure of 140 MED. this translates to an annual WA dose a high-pressure WA suubed.
of 7700 kJ/m2. For a frequent tanner with an annti exposure .
of 350 MED, this translates to an annti WA desk of Effective annual doses from sunlamps versus the sun
19 250 kT/m2. It should’be mentioned that if the majokty of ‘A similar analysis can be performed to compare the effective
an indiyidkl’s exposure occqs at times &fore lo:00 A.M.. . doses. .In Table 5 the annual effective doses from the sun

.
were determined by multiplying the re&p&ztive cffeckve dose &i&les of netier technology hi the sunlamp in&&y that,
per MED times the number of annual MED for each type although not widely used today, may represent a’ trend to
of tanner, typical or frecluent. Then. the ;eIative annual ef- lampi of higher dose rate. ..
,fective dose from sunlamp exposure was cgmpared to the * The effective dose rates for typical WA sunlamps (lamps
total annual effective .dose from the sun, for both a typical 14) are similar to that of the sun when both the erythema
tanner/sunlamp user and for the frequent t~~er@unIamp and the SCC action spectra are used (Table 2). As expected,
user. Applying’the SCC action spe&ruth results in suniamp these effective dose rates fern both the.liigher UVB-emit-
exposure cotitibuting approximately 0.20 times. the annul .ting high-speed &bed and FS lamp.exceed that ?f ihe.sup.
solar effective dose for the trpicaI user. For-&e frequent &ser Although Fe high-pressure WA ‘sunbed emits less than
the SCd-effeetive.do~ from sunlamp exposure is approxi: 0.1% UVB, the large quantity of WA radiation p+eni con-
mately equal t0.tha.t from-so& exposure for all of the.sun- tributes significantly to the weighted integral. and the resul-
lamps: tant effective dose rate ti very similar to that of the sun &hen
If the calculati&s are performed using the XFM action both the erytheG and SCC &ion spect& are used. The
‘spectrum, the rem&s are very similar to the analysis of WA absolute magnit@e of the effective IoFM dose rate is much
exposure. For the typical tanner/sunlamp user receiving 140 larger than the erythema or‘ $CC dose rate because the
MED/year. from the sun the XFM dose tim s&u exposure weighting. factors b the WA region of :the XFM action
is approxinjately 1500. kf/mf, Thus 20 visi& to a tahning speceum are two to three ordw of magnitude high&r than
salon at 2 MED’per session can contribute 0.3&L3 times *the other t&o action spectra. This fact renders all but the
an individual’s annual s&u dose for lamps l-4 and as much . FS lamp signiiicantly more, effective than the sun when the
as 2.8 times for 20 ,sessions‘under a high-pressure WA sun- XFM action spectmm is used, especially the high-pre&ure .
be+ In the &se of a frequent tanner/sunk&p user; 100 visits WA sunbed that has an XFM dose rate over 12 times that
to ! a ta&ing salon at ‘4 MED per se&ion can potentially ‘ofthesun.
contribute 1.6-5.2 times an individual’s annual sol& dose Once the results are normalized co i MED flable 3). both ‘.
for lamps 14 and. as much & lr times for 100 sessions the UVB doses and the SCC doses from sunlamps are lower
under a high-presiure WA sunbed. than the solar doses. &ile the WA and XFM doses are
significantly h&her. Lamp 2 from the US market is the ex-
DlSCiJSSlOi ception to this, as it appears to be most sirnil& to the Sun in.
Our measurements indicate that the WB ‘dose rates from its UV spectral content. For the high-speed sunbed, the SCC-
typical WA Buorescent’ sunlamps, such as lamps. 14. are effective dose is, now less than ‘that from.the sun, while the
similar to that of noontime, summer sun (latitude 3&9“N), XFM-effective dose is only twice that of the sun. However,
while the WA dose rates are two to t&e4 times higher. The the high-pressure UVA sunbed still stands out from the rest
two US sunlamps chosen for tliis study have significantly of the sunlamps with its UVA and ‘XFM dose at 10 times
different em$sion spectra, with lamp 1 emitting 99% UVA and 9.8 times that of the sun, respectively. As expected, the
and lamp 2 emitting 95.7% UVA. which is more similar to SCC doses track the UVB doses and the XFM doses track
the sun. A recentIy available high-speed sunbed allows tan- the UVA doses. Thus,.the unweighted doses could be used
ning in a much shorter period of time, with a UVB dose rate as a surrogate for. the effective doses in an. analysis of
of two times and a UVA dose.rate six times that of summer sources with emission spectra similar to the sources evaI&
sun. The high-pressure UVA sunbed emits the highest. UVA ated in this study.
dose rate of 13 times that of summer sun. These last two are Although the UVA dose rates from lamps 3 and 4 are
.‘.‘......, . “i.2
“C

Photoch&nistry and Photobiology, 1998, 68(l) ,69

higher than the UVA dose rates from lamps 1 and 2. the more likely to get a bum from a UVB sunlamp because the
UVA doses per MED and the effective doses pet MED fall time to reach an MED with a UVB sunlamp is much shorter
within the same &nge. Thus, there appear to be no signifi- and therefore more likely to be exceeded inadvertently dur-
cant differences between sunlamps marketed in the US and ing a tanning session. This potential could be reduced by
those m‘arketed in Sweden that would account for the high lowering the dose rate and thereby increasing the time to
odds ratios reported in the Swedish epidemiologic study (5). erythema. In addition, there are remaining controversies re-
However, the available annual erythemally effective solar garding the importance of bums to the etiology of melano-
dose in Stockholm (59”N) is less than 0.60 of what is avail- ma. Some researchers have suggested that only those expo-
able in Washington, DC (24). Thus, although the UVA dose sures that result in a bum may be important (8.26). However,
rates are not that different in the two locations (25). an ex- there is evidence, particularly from Australia, indicating that
amination of annual cumulative doses would demqnstrate total cumulative overdosage of sunlight-not necessarilyre-
that sunlamp exposure contributes a significantly larger pro- sulting in burns-is also important (27). If more data be-
portion of an individual’s annual UV dose in Sweden com- come available regarding the correct action spectrum and
parod to Washington, DC, assuming similar solar exposure dose response model for melanoma, the comparative risk
patterns. Thus if cumulative, intense exposures are important levels from exposure to sunlamps of differing spectral q&put
to melanoma induction, the high odds ratios reported in the can be quantified.
Swedish epidemiologic study (5) could be expla&d by this In generating the relative effective dpse in Table 5, it was
difference between sumamp exposure and environmental ex- assumed that all exposure contributes equally to the total
posure. In other wOrds, for individuals residing in geograph- effective dose. However, a comparison of‘total cumulative
ical areas of iow solar exposure, sunlamp exposure cOoId dose received annually from sunlamps and espeeiazly the-sun
constitute a greater relative risk than for individuals residing may not ‘be a valid method of risk analysis for melanoma.
in geographical areas’of high solar exposure. One might argue that frequent users of sunlamps ore similar
The res&.s in Table 4 p&it to the fact that exposure to to outdoor workers who do not demonstrate a $$icantly
sunlamps can significantly increase an individual’s total an- ‘increas&i risk of melanoma over indoor workers ‘(28-30).
nual UVA dose, but this is highly dependent on exposure However, the emission speotrum, UV dose rate and exposure
frequency. For l&ps 1 and 3, the typical .user’is effectively pattern of sunlamps are different from that of the su& so the
doubling their anrtu~ UVA dose by adding 2Q sunlamp ses- experience with outdoor workers cannot be dhectly extrap-
sions to their, typical yearly solar exposure. Using lamp 2 olated to the situation with indoor workers who use sun-
will increase the yearly UVA dose by only a factor of 0.30, lamps. The etiology of melanoma depends strongly’on ge:
whereas using a high-pressure WA sunbed v@I increase the netic factors mat may influence an individtis exposure pat-
yearly WA dose- to nearly four times what. it would have tern as well In fact, in studies showing ‘indoor workers to
been from solar exposure alone. For the frequent user, the be at higher risk ,than outdoor workers, this dlffer&e& *mrisk
situation looks significantly worse, even though a base solar is reduced once host factors like *skin color are taken into
dose of 2.5 times that of the typicai tanner is assumed. In account (27). In addition, there may be a protective effect
this case, the annual UVA dose can he increased by almost afforded by regular exposure to full-spectrum solar radiation,
a factor of 6 for a 99.0% WA sunlamp and by as much as such asvitamin D production (29).
a factor of 13 for the high-pressure WA sunbed. Consid- The data reported here indicate that modest exposures to
ering that the base solar WA’ dose assumed is 19250 k.I/ commonly used sunlamps would increase ti indivi&mI’s. air- ..
m*, a frequent user could receive up to 250000 kirm* of nual WA dose by 0.31-1.2 times. However, quite @ti.fi-
WA per year (eight times the dose for a ty&al user) if a . cant (>lO times.higher) W exposures can be obtained for
high-pressure UVA sunbed were used 100 times/year at 4 frequent use of newly ‘marketed sunlamps like the high-pres-
MEDlsession in addition to the solar dose’ of 330 MEDs. sure WA sunbed. The resulting annual effective doses ex-
+The results in Table 5 indicate that the magnitude of rel- hibit an even larger, variation than the aual WA doses.
ative contribution of sunlamp exposure to total annual ex- Depending on which action spectrum is. chosen--SCC or
posure is highly dependent on which.action spectrum is cho- XFM-and which exposure pattern-typical or frequent-
sen. If the SCC action spectrum is applia the annual ef- the range in annual, effective doses can fall anywhere be-
fective doses are increased by only a factor of approximately tween a 0.17 increase to a 1 l-fold increase over what would
0.20 over what would be received from the sun alone for a be received from the sun. Until more information is avaiIable
typical sunlamp use of 20 sessions/year. For the frequent regarding the correct action spectrum and dose response for
user, this increases to approximately 0.8. If the XFM action melanoma in humans, limiting one’s exposure to both SWI-
spectrum is applied, the contribution from lamps 14 ranges lamps and the sun would appear to be the most effective
from 0.38 to 5.2 times the solar dose, &pending on the way to reduce one’s risk.
pattern of use. This relative increased dose goes up to 11
times for the high-pressure UVA sunbed for the frequent Acknowledgements-The authors gratefully acknowledge the critical
review and helpful comments contributed by Dr. Barbara Zmudzka
user. Thus, the choice of action spectrum is critical in de- and Dr. David Lytle in preparation of this manuscript.
termining the relative risk of sunlamp use.
If the XFM action spectrum proves to be accurate for REFERENCES
humans, then exposure to UVA sunlamps could contribute
1. Weinstock. M. A. (1993) Epidemiology of melanoma. In Cur-
a significantly highec risk for melanoma development than rem Research and Ciinical Management of Melanoma (Edited
does exposure to the sun or exposure to the older UVB-type by L. Nathanson), pp. 29-56. Kluwer Academic Publishers,
of sunlamp. However, in reality, a sunlamp user may be Norwall, MA.
70 Sharon A. Miller et al.

2. Armstrong, 6. K. and A. Kricker (1993) How much inelanoma Technical Report, Contract DAJA37-68-G1017, European Re-
is caused by sun ejtposure? Melanoma Rex 3, 395-401. ;“$&Ii. O$iCe, US Army, London.
3. Moan, J. and A.‘Dahlbxk (1993) Ultraviolet radiation and &ih 17. I.J&&. F. (isrii) Man and ultraviolet radiation. In Human EC-
cancer: epid&Gological data from Scandinavia. In &:nviron~ncn- posure to Ultraviolet Radiation-Risks and Regulations (Edited
101 UV Plu~cobiolo~y (Edited by A. R. Young), pp. 255-293. by W. F. Passchier and B. F. M. Bosnjakovic). pp. 3-17. El-
Plenum Press, New York. sevicr Science Publishers B.V.. Amsterdam.
4. Swcrdlow, A. J.. I. S. C. English, R. M. Mac Kit, C. 1. 0’ 18. Challoner. A. V. I.. 0. Corless, A. Davis, G. H. Deane. B. L.
Doherty. J. A. A. Hunter, J. Clark and D. J. Hole (1988) Flu- Diffey, S. P. Gupta and I. A. Magnus (1976) Personal monitor-
orescent lights, ultraviolet lamps, and risk of cutaneous meta- ing of exposure to ultraviolet radiation. Clin. Exp. Dermatof. 1.
noma. Br. Med. J. 297, 647-650. 175-179.
5. Westerdahl, J.. H. Olsson, A. Masback, C. Ingyar, N. Jonsson. 19. Leach. J. F.. V. E. McLeod, A. R. Pingstone. A. Davis and G.
L. Brandt. P. Jonsson and T. Moller (1994) Use of sunbcds or H. Deane ( 1978) Measurements of the ultraviolet doses received
sunlamps and malignant melanoma in southern Sweden. Am. J. by office &orlcers. CIin Exp. Dermatol. 3, 77-79.
Epidemiol. 140, 69 l-699. 20. Scotto. I.. T. R. Fears and J. F. Fraumeni. Jr. (1983) Incidence
6. Walter, S. D.. L. D. M&rett, L. From, C. Hertzman. H. S. Shan- of no&&noma skin cancer in the United St&.. NIH Publi- .
non and P. .Roy (1990) The association of cutaneous malignant cation no. 83-2433.
melanoma with the use of sunbeds and sunlamps. Am J. Epi- 21. Lyde. C. D.; W. H. Cyr. J. 2 Beer, S. A. Miller. R. H. J&es.
demiol. 131. 232-243. R I. La&y. M. E. Jacobs. R G. IcImzMnk c. M. Sha.rlat~.
.7. Autier. P.. I. F. Dare. F. Lcjeune, K. F. Kotlmel. 0. GeffeIer, D. Gay&. F. & & Gruijl and J. c van der Leun (‘199211993)
P. Hille. J. Cesarini. D. Lienard, A. Liabeuf, M.- J&&ttc, P. An csthhation of squamous cell carcinoma risk fmm ultraviolet
Chemaly. K. Hakim, A. Kocln and U. R K&b&g (1994) Cu- radiation emitted by fluotcscent lamps. Photodevnatol. Pho-
taneous malighant meI+noma and exposure to’sunlampir or sun- toimmunoL Photomed 9.268-274.
beds: ” EORTC multicenter &sc-cot&ol study ic Belgium, 22. La&o. 0. and B. L. Diiey (1983) Natural U\i-B radiation re-
France and Gcrmai~y. Iti J. Gmcer,S8,8G9~13. ceived by people with outdoor, indoor. ana mixed occupations
8. Osterlind, A., M. A. Tucker, B1 J. Stone and 0. M. Jensen and UVB treatment of psoriasis. Clin. ?&p. DermatoL 8. 279-
(1988) The Danish case-control study of cutaneous malignant 285.
rhel+oma. IL impo$ance of W-light exposure. Iti. 1 Cancer 23. Cb. Food and Drug Administration. (1986) Policy dn nqximum
timer intervals and exposure -xhedule for sui~lamps. August 21,- .
42.3 19-324.
1986, Department of Health and Human Services.: Food and .
9. Sctlow, R B.. E. Grist, ‘K. Thomson and A. D. ‘&&head.
(1993) Wavelengths effective in ‘induction of malignant .mela- Dtig “Administration, C&&i for bevices and Radiological
noma: Proc. NatL ,Acad Sci. USA 90.66664670. Health, Rockvillc, MD.
24. Josefsson, W. (1996) Five years of solar W-radiation mouicoc-
. 10. Ley. R D. (1997) Ultzavi&t tad&ion A-induced precursors of
ing in Swedct~ SMHI F&ports of Meteorology and Cliitoroejr.
melanoma in Monodelphis &me&. Gzncer Res. 57. 3682- No. 71. Swedish Meteorol&ical and HydrologIcal Institute. S-.
3684.
60176 Non-koping, Sweden,
Il. CER escarch Note (1987) A reference action spcctxum for III- 25. We-s&, U. (1993) W-cqksucc and oti~e monitoring .svith a
traviolei induced erytheti iii timnan &in. CIE J. 6; 17-22. .dual baudpass &x&u WA- rn& in Stockhqlm &ice 1989.
l-i. De Gmijl, F. R and J. C v&a der Lemi (l-4) I&tin&e of the In Fmmziers of Photobtol& (Edited by Shima et aL). pp. 5 19-
wavelength dependency of ultraviolet carcinogen&s in humans . 522.. l!?Isevicr Scikncc Put&&ecs~B,.V.. mecdarn
and ,its relevanti to the cisk assessmentof a stqtosphetic ozom 26. .GN&I, A.. V&stid, C. Bain and J. Alexander (1982) S~mnbum
depletion. Heal& Phys. 67,319-;325. and mzlignan~ rnelaw~ Br. 1. Cancer 51, 393-397.
13. Diffey. B. L. (1986) Use of WA sunbeds $or c&u& tanning. 27; Boyle, P.. P. Maisonn&ve and J.-F; Dare .(X995) Epidemiology
Br. 3. DermatoL ll5, 67-76. of malignant melanoma. Br. Mea! J. 51,X&547.
14. Sliney. D. and M. Wolb&sht (1980) Safty wit& f.usqs and 28. Green, k and D. Baaistutta (1990) Incidence and determinanw
Other Optical Sources, A Comprehensie Handbook. p. 204. of skin &ncer in a high-risk &&alian population ht. L Con-
Plenum Pceqs, New York. cer 46.356-361.
15. Diffey. B. L,(1979)‘l%e calcul+ion of the spectral diifributi~n 29. Garland. F. C. and C. F. Garland (199O),GccupationaI suuligbt
of natural ultraviolet radiation under cleq day conditions. Phys. exposure and melanoma in the. U.S. Navy. Arck.. Enviru~
Med BioL 22.309-316. ‘Health 45.2x51-267.
16. Bener, P. (1972) Approximate valqes of intensity of natural W . . SO. Let, I. A. H, and D. &rick&d (1980) Malignant meIanoma:
radiation for different amounts’ df atmospheric ozone. Final social status and outdoor work. Br. J. Cancer 41.757-763.
9 1040.20 21 CFRCh, I i4-l-d0 Editton) Food and Drug AdmInIstration, HHS $la40.30
sequential exposures and maximum ex- .name of the manufacturer and month compatible protective eyewear, ultra- ception of the tungsten filament self-
posure time(s) in minutes. and year of manufacture affixed or in- violet lamps, timers, reflectors, and fil- ballasted mercury vapor lamp, incor-
(v) A statement of the time it may scribid on the exterior surfaoe of the ters, and which will, if installed or used porating a high-pressure arc discharge
take before the expected results ap- lamp may be expressed in code or sym- as instructed, result in continued com- tube that has a fill consisting pri-
pear. bols, if the * manufacturer has pre- pliance with the standard. marily of mercury and that is con-
(vi) Designation of the ultraviolet viously supplied the Director, Office. of (2) LWaviofet lamps! The users’ ip- tained within an outer envelope.
lamp type to be used in the product. Compliance (HFZ300), Uenter for De- s&&ions for an ultraviolet lamp not (2) Advertisement means any catalog,
(2) Labels for ultraviolet lam&. Each vices andXWiiologica1 Health, withthe acoompanying a sunlamp product shall specification sheet, price list, and any
ultraviolet iamp shall have - a label key to such code or symbols and the lo- contain: other descriptive or commercial bro-
which contains: cation of the coded information or (i) A reproduotion of the label(s) re- chure and literature, including video-
(i) The words “SunlampDANGEF+ symbols on the ultravfolet lamp. .?l?he quired in paragraphs (d)(l)(i) and (2) of tape and film, pertainiiig.to high-inten-
Ultraviolet radiation. Follow instruc- label .or tag affixed or inscribed on .the. this section, ‘prominently displayed at sity mercury vapor discharge lamps.
tions.” lamp packaging may provide either the the beginning of the instructions. (3) Packaging means any lamp carton,
(ii) The model identification. month and year of manufacture with- (ii). A warning that the instructions outer wrapping, or other means of con-
(iii) The words “Use ONLY in fixture out abbreviation, or information to accompanying the sunlamp product tainment that is intended for the stor-
equipped with a timer.” allow the date to be readily decoded, should always be followed to avoid or age, shipment, or display of a high-ln-
(3) Lube1 specifications. (i) Any label (v) A label may contain statements to minimize potential injury. tenslty mercury vapor lamp and is in-
prescrfbed in this paragraph for sun- .or illustrations in addition to those re- (iii) A clear identification. by brand tended to identify the contents or rec-
lamp products shall be permanently af- quired by this paragraph if the’ addl- and model designation of all lamp mod- ommend its use.
fixed or inscribed on an exterior sur- tional.statements are not false or mis- ,els for which replacement lambs are (4) Outer envefone means the lamp ele-
face of the product when fully assem- leading in any particular; e.g., if they promoted, if applicable. ment, usually glass; surrounding a
bled for use so as to be legible and do not diminish the.imoact ---.--- cf the
~-~ re-
~- (f) Test for determinatfon of compltance. high-pressure arc discharge tube, that,
readily accessible to view by the person quired statements: and are not prohib- Tests on which certification pursuant. when intact. attsnuatas the emission
being exposed immediately -. before the ited by this chap;ter. to $1010.2is based’shall account for all of shortwave’ultraviolet radiation.
use of the product. (e) &structfon.?~to be provided to users. ‘errors and statistical uncertainties in (5) Shortwave ultraviolet radiation
(ii) Any label prescribed in this para- Each manufacturer .of a sunlamp prod- the prodess and, wherever applicable, means ultraviolet radiation with wave-
graph for ultraviolet lamps shall be uct and ultraGiolef lamp shall provide. for changes in radiation emission or lengths shorter than 320nanometers.
permanently affixed or inscribed on the or cause to be provided to purchasers,. *degradation. in radiation safety with (6) Cumulative operating ‘time means
product SO as to be legible and readily and, upon request, to others at a cost age ‘of the product. Measurements for the sum of the times during which elec-
accessible to view. not to exceed the oost of’publioation oetilfication purposes shall be made tric current passes through the high-
(iii) If the size, configuration, design; and distribution, adequate fnstruations under those operational conditions, pressure arc discharge.
or function of the sunlamp product or for use to avoid or to minimize poten- 1amD voltage, ourrent, and position as (7) Self-ertfnguishfng tamp means.. a
ultraviolet lamp would preclude com- tial injury to. the user, including the recdmmend~d by the nianufaoturer. high-intensity mercury vapor dis-
pllance -with the requirements for any following technical and safety informa- For these measurefnents, the meas- charge lamp that is intended to comply
required label or would render the re- tion as applicable:- uring instrument shall be positioned at with the requirements of paragraph
quired wording of such label inappro- (1) Sunlamp ‘products. The users’ in- the recommended exposure position (d)(l) of this section as applicable.
, . priate or ineffective, or would render rttruotions for a sunlamp prokot shall and so oriented as to result’inthe max- (8) Reference ballast is an inductive re-
.the required label unnecessary, the Di- contain: .*. imum detection of the radiation by the actor designed to have the operating
rector, Office of Compliance (HFZ300), (1) A reproduotioa of the label(s) re- instrument. characteristics as listed in Section I in
Center for Devices and Radiological .quired in paragraph (d)(l) of this sec- (The information oollebtion requirement8 the American National Standard Sgeci-
Health, on the Center’s own initiative tion prominently displayed at tho be- contained in pwagraphr, (d) and (e) were ag fications for High-Intensity Discharge
or upon written application by the . ginning of the instructions.. proved by the Offloe of Management and Lamp Reference Ballasts (ANSI C82.5
manufacturer, may approve. alternate (ii). A statement of the maximum Budget under control number W9-0195) 1977)’ or its equivalent.
means of providing such label(s), number of people who may be exposed (,50 FR 96550, Sept. 6,1988] (c) General requirements for all lamps.
alernate wording for such label(s), or to the product at the same’ timeand a (1) Each high-intensity mercury vapor
deletion, as applicable. warning that, only thit number of pro- 5 1030.30 High-intensity mercury discharge lamp shall:
(iv) In lieu of permanently affixing. or tective eyewear has been provided. vapor discharge lamps. (i) Meet the requirements of either
inscribing tags or labels on the ultra- (iii) Xnstructions for the proper oper- (h) Applicability. The provisions of paragraph (d) or paragraph (e) of this
violet lamp as required by §51010,2(b) ationof the product inoluding the func- this section itpply to any high-inten- section; and
and 1010.3(a),the manfacturqr of the ul- tibn, .use, and setting of the timer ahd sity rnerc\rJ vapor discharge lamp (ii) Be permanently labeled or
travlolet lamp may permanently affix other controls, and the use of proteo- . .that is designed, intended, or promoted marked in such a manner that the
or inscribe such required tags or labels, tive eyewear. for illumination purposes andis manu- name of the manufacturer and the
on the lamp packaging uniquely associ- (iv) Instructions for determining the factured or assembled after March 7, month and year of manufacture of the
ated with the lamp, if the name of the correct exposure time and schedule for 1980. except as desoribed in paragraph lamp can be determined on an intact
manufacturer and month and year. of ‘persons acoording to skin tgpe. (d)(i#ii) of this seotion. lamp and after the outer envelope of
manufacture are permanently affixed (v) Instruotions for obtaining repairs (b) Deffnftiq.s. (1) HigWntensitu mer-
or inscribed on the exterior~surface of and recommended replacement compo- cusy vapor, dfschurge Zamp means any 1 Copiesare available from American Na-
the ultraviolet lamp so as to be legible nents and accessories W&h are com- lamp $ncluding t)ny “mercury vapor” tional Standards Institute, 1430Broadway, *
and readily accessible to view, The patible’ “with the product, incla’ding and “metal halide,” lamp, with the ex- New York, NY 10018.
-tt
626 627
ci
- ~002/006 .
12:03 '8'301 594 6775 FDA DLS
4+G
09/04/98 12:03 ?%301 594 6775 FDA DLS @I003/006
..
-m. . ..-

The formula for decenninirig the recommended maximum exposure time,
"1:m- in seconds is: .: ._ --.

Tm = It%&/"' vhe,re standard %Q+@ A 4>9J/g2 at 296niu ‘
J. - weighting factor .
'. .
.+ = irradiance in W/M2 ..
-,t 3) The recommended exposure scSedule should provfde for exposures
of no more than 0.75 HZD three times.the first week, gradually
increising.the exposure the f&Sowing weeks until maximum tanning
has occurred (approximately fouT' weeks total) and then provide for
maintenance of a tan by biwe&ly or week19 exposures of up to
. four(4) MEW or four(L) MM!.Js,vhichever.3.s less.

CDBWbeH.eves chat the above criteria balances the ‘,eid to IlmLt .azute (and
delayed) damages from unintoctioaally long exposure and the need to pr04.d~
3or single exposure durations adequate to achieve -and maintain a taz.

t Lt . EFFECTIVE UPON PUBLiCAl-ION
FDC date State City Airport qDC No. StAP
-- --
04/29/99 . . . .. . . PA STATE COLLEGE ........... UNIVERSITY PARK ............................. i 9/2846 JOWDME RNAV or GPS RWy 6
AMDT 6
04l29l99 . . .. .. PA STATE COLLEGE ........... UNIVERSITY PARK ............................. 912847 VOR or GPS-B AMOT 9
o4429/99 . . .._.. WI APPLETON ..................... OUTAGAMIE COUNTY REGIONAL ... 912851 ILS RWY 3, AMDT 16C
04/30/99 _...... MO BUTLER _._....................... BUTLER MEMORIAL ........................... g/2875 GPS RWY 18. ORIG
04/30/99 . .. .. .. TX AUSTIN ........................... AUSTIN-BERGSTROM INTL ............... 9l2879 ILS RWY 354 AMDT 1
04/3of.99 . .. . . . . TX AUSTIN ........................... AUSTIN-BERGSTROM INTL .- ....... i.. .. 912880 GPS RWY 35L, AMDT 1
o4aoi99 . .. .. . . TX AUSTIN ........................... AUSTIN-BERGSTROM INTL ............... 9/28til GPS RWY 17R. AMDT 1
04L30/99 . .. . . . . TX AUSTlN ........................... AUSTIN-BERGSTROM INTL ............... 9m382 ILS RWY l7R, AMDT 1
o!Y1/99 . . ..-.... MANCHESTER ............... MANCHESTER ................ . .................. 9/3102 ILS RWY 2. AhiDT 2
05/1/99 .... . .. .. ii MANCHESTER .......... :_... MANCHESTER ._................-- ............. 913103 ILS RWY 35. AMDT 19
osm4l99 . .. .. .. CHICAGO/AURORA ....... AURORA MUNI i.. ...... .__......-._............ t 9l2970 VOR or GPS-A AMDT IA
osm5m9 _- I; CHICAGO/AURORA ._..... AURO.RA MUNI . . . ........... . -..?.s7 . 912983 ILSRWY9,AMDTlA :_
05m6l99 -.--.. MIDDLETO%!N .. .._-..._._... HOOK flEL0 MUNI ......... . . . ;.I..._ ....... 9l3009 LOC RWY 23, AMOT 7S
05%.x/99 . .--.. . :“H MIDDLETOWN .. .._-.......... HOOK FlEu, MUNI .. . ..... . .. . ........ . ... 9B510 NOB or GPS RVVY 23, AMOT 8A . ..
0!5fo6/99 .. .. . .. OH MIDDLFTOWN ._... ........... HOOK RELD MUNI ... .._...... -.. . . ...... . . g/301 1 ND8 or GPS-A. A&lOT 2A
05llof99 . . ... .. MN WGRTHINGTON ............. WORTHINGTON MUNI . . .. -. ........ 9/3066 NOB or GPS Rw 29. ORIG
05/10/99 A..” WORTHINGTON .... .._...... WORTHlf4GTON MUNI . . . . . . -.. . IIS RWY 29, ORIG.
osm/99 . . ..“I t!! RICHMOND ....... . .. . ......... CHESTERFIELD COUNTY --r-i. 9m74 NbSorGPSRWY33,AMDT7A -
- 050 O/99 ..*.... VA RICHMONO ..................... CHESTERRELO COUNTY ...... i.r. 9l3075 VOR!DME or GPS RWY 15. ORlG -
‘05110199 ....... VA : RICHMOND ............. .._..... CHESTERFlELD C@JNTY. ... . . e _ ...... 9f3082 ILS RWY33,ORlG ‘. .
L - I
. ,
. .
[FR Dot. 9942949 Piled 5-20-99; 8:45 am) EFFECTIVE DATES: This regulation is glyceryl aminobenzoate. lawsone with :
SlLUiG CODE 4910-Xi-f4 effective May 21.2001 for parts 310. dihydroqacetone (interest was
352. and 700 and is effective May 22. subsequently shown in developing a
2OOO’forpart 740: monograph for lawsone and
DEPARTMENTOF HEALTH AND FOR FUR&ER INFORMATION CONTACT: John dihyd;oxyacetone) . and red pe@oLatum. ._
HUMAN SEFiVlCES D. Lipnicki; Center for Drug Evaluatien : The agency also reiterated th$ a!
and Research (HFDZj60). Food &nd ‘. sunscrqen ingredients must have a USP . ‘1
Food and. Drug Admit&ration Drug.Administration. 5600 Fishers monograph before being included’ in the
Lani. Rockville. MD 20857.301-827- final monograph for OTC sunscreen .
21 CFR Parts 310, &2,700, and 746 2222. drug products. This ffn$ ‘i$le+includes
SUPPLEMENTARY INFORMATION: ; those sunscreen ingredients that,have
[Docket No. 78N-O038] USP monographs.
I. Introduction In the Federal Register of September.
RIN 09104AOl 16.1996 (61 FR 48645). the agency
In the Federal Register of August 25.
S&screen Drug Products For Over- 1978 (43 FR 38206). FDA published, amended the proposed rule to include
The-Counter Human Use; Final under §33O;lO(a)(6) (21 CFR avobenzone as a single ingredient and Ln
Monograph 330.10(a)(6)), an advance noticeof combination withcertaln other .
proposed iulemaking (ANPRM) to sunscreen ingredients (interim
.AGENCy: Food and Drug Administration. establish a monograph for Q’l’C marketing was allowed in‘the Fede,d
HHS, sunscreen drug products, together with Register of April 30. 1997 (62 FR
@XIO~~ Final rule. .the recommendations of the Advisory 23350)). In the Federal Register of .
Review Panel on OTC Topical October 22.1998 (63 FR 56584). the
SUMMARY: The Food and Drug Analgesic. Antirheumatic, Otic, Burn, agency proposed to amend the tentative
Administration (FDA) is issuing a ftnal and Sunburn Prevention Drug Products final monographto include zinc oxide. .’
rule in the form of a final monograph (the Panel), which was the advisory as a single mgredient and in
establishing conditions under which review panel that evaluated data on the combination with any proposed
over-the-counter (OTC) sunscreen drug active ingredients m this &g class.. The f Category I sunscreen active ingredient
products are generally recognized as agency’s proposed regulation for OTC except avobenzone.
safe and effective and not misbranded as sunscreen drug products, in the form of In the Federal Register of April 5.
part of FDA’s ongoing review of OTC a tentative final monograph, was 1994 (59 FR 16942). the agency
drug products. FDA is issuing this final published in the Federal Register of reopened the administrative record and
rule after considering public comments May 12. 1993 (58 FR 28194). announced a public meeting to discuss
on the agency’s proposed regulation, In the Federal Register of June 8. 1994 ultraviolet A (UVA) radiation claims
which was issued In the form of a (59 FR 29706). the agency proposed to and testing procedures. In the Federal
tentative flnal monograph, and new data amend the tentative Enal monograph Register of August 15.1996 (61 FR
and information on sunscreen ,drug (and reopened the comment period until 42398). the agency reopened the
products that have come to the agency’s August 22. 1994) to remove five administrative record and announced a
attentlon. FDA is also issuing final rules sunscreen ingredients because of a lack public meeting to discuss the
regarding the labeling of certain of interest in establishing United States photochemistry and photobiology of
cosmetic products to inform consumers Pharmacopeia (USP) monographs: sunscreens.
that these products do not provide Digalloyl trioleate, ethyl 4- This final monograph compiet& the
protection from the sun. [bis(hydroxypropyl)] aminob&zoate, tentative final monograph except for
Federal Register/ Vol. 64. No. 98/Friday, May 2 1. 19991Rules and Regulations 27667
certain testing issues and UVA labeling, submission of a formal petition by an ;pecified when the final rule for testing
which the agency will discuss in future interested party. xocedures publishes.
issues of the Federal Register. Until The agency has included these data 2. Several comments recommended
then, UVA labeling may continue in and information in the administrative nodifications to the definition of
accord with the tentative final record and addressed them in [his ninimal erythema dose (MED) in
monograph and its amendments. The document. The agency has considered proposed 5 352.3(a). Some comments
agency advises that on or after May 2 I, the request for an oral hearing in its objected to the presumption that
200 1. no OTC drug product that is response to the comment and believes it erythema is a “diffusing” reaction that
subject to the monograph and that has adeauatelv responded to the starts from within the exposed site and
contains a nonmonograph*condition manufacturer-and ihat a hearing is not moves outward in a dose dependent
may be initially introduced or initially needed. As discussed in section ILC. manner. t.e... “redness reaching the
delivered for introduction into interstate comment 29 of this document. the borders of the exposure site.” Other
commerce unless it is the subject of an agency is allowing the marketing of OTC comments asserted that the definition is
approved new drug application or sunscreen drug products with SPF too limiting because it may not be’
abbreviated new drug aoolication. values above 30 under one collective appropriate for all solar simulator
Further, any OTC dig pioducf subject term (i.e., “30 plus” or “30 +“). The configurations (e.g.. no template). Many
to this monograph that is repackaged or agency will also consider including comments recommended the deflnltlon
relabeled after the effective date of the labeling in the monograph with actual of MED used by the European Trade
monograph must be in compliance with label SPF values on products with SPF Association COLIPA (Ref.5): “The,
the,monograph regardless of the date the values over 30 when adequate data are quantity of radiant energy required to
product __ was initially introduced or submitted to substantiate a testing produce the first perceptible.
initially delivered for introduction into . procedure applicable to SPF values over uririmbiguous redness reaction with- .
interstate commerce. Manufaeturersaie 36. clearly.defined borders.” Another
encouraged to comply voluntarily as ._, comment recommended “erythema-
soon as possible. IL The Agency’s Conclusions on the
Commef+ - effective ultraviolet radiation*’ in place ..
In response to the proposed rule on of “radiant energy.”
OTC sunscreen drug products and A. GenerarCommen& on OTC . The agency agrees that the proposed .
subsequent reopenings of the Sunscreefi~Drug Pqducts definition of MED should be modified
administrativerecord, the agency
received 433 comments. The comments 1: Several comments asked that the for the reasons discussed by the
included four petitions (Refs. 1 through . agency eltl+r exempt~currently. comments and is revising §352.3(a) in
4) requesting considerationpf sunscreen mtiketed sunscreen‘products’ from the : this final rule. as follows: “MinJmal
ingredients that have en marketed in requirement for redetermining the SPF ‘erythema dose &ED). The quantity of
Europe but not in the 8 nited States. The or ‘provide a Z-year implementation erythema-effective energy (&pres+l in
stati of these petitions is dii&~~ed in period. One comment requested a 3year Joules per square meter) required to .
section KC. comment ‘13 of thii implementation period. The commenti produce the fiist perceptible redness -
document. One manufacturer requested contended that the proposed 1Zmonth reaction with clearly defined borders.”
an oral hearing before the Commissioner implementation period would result in The agency considers this definition
of Food and Drugs if the agency lost business tid a serious economic broad enough to’encompass tests
mandated a limit on sun protection . hardship for manufacturers; estimated conducted with solar simulator
factor (SPF) values in thii fir@ rule. to-be 35 million dollars or configurations with no template and
,cOpies of the information considered by. reformulating, retesting. and relabeling consistent with COLIPA’s definltlon. .
the _.Panel. the comments and,petitions. sunscreen
-_ products. __ - 3. One comment noted that the
and the hearing request are on public ‘l‘he agency agrees with the comments wavelength ranges for WA, WB. and’
display in the Dockets Management that the proposed l&month ‘. WC radiation in the tentitive final,
Branch (HFA-305). Food and Drug implementation period may cause monograph d&red from the official
Adm1ni&ation. 5636 Fishers La&, rm. undue. economic-burden on some ranges of the Commission International
,1061, Rockville. MD 20852. Ail “OTC manufacturers of these products without de L’Ecl&age (CIE). which are: (1).
Volumes” cited throughout this a corresponding benefit to consumers WC-radiation of less than 280 :
document refer to’information on public (see section VII of this document). As nanometers (run). (2) WB-286 to 315
display. discussed in section VII. a 24-month nm. and (3) WA-3 15 to. 406 nm. The
A number of comments were filed in effective datewould allow most firms to comment mentioned the agreement
the Dockets Management Branch after relabel products during a normal reached at the 1IthIntemational
the dates the administrative record had relabeling cycle without incurring Congresson Photobiology (Ref. 6) on the
officially closed. The agency has additional costs. Accordingly, the final short wavelength end of WB radiation
considered these comments as rule will be effective 24 months from (280 or 290 nm) and suggested that the
“feedback” communicatiqns under the the date of this publication. Because this scientific evidence sUpports 320 nmas
OTC drug review procedures, as final rule provides testing procedures the long-wavelength boundary of UVB
discussed in the Federal Register of that were proposed in the tentative final radiation,
September 29. 1981 (46 FR 47740). and monograph, currently marketed The agency agrees with the comment.
clarified in the Federal Register of April .products that have already been tested that the scientific evidence supports 320
1. 1983 (48 FR 14050). When by those procedures wit1 not need to be nm as the long-wavelength boundary of
“feedback’* material submitted after an retested. However, sunscreen products UVB radiation. However, the short-
administrative record has.officially that have not been tested will need to wavelength boundary for UVB radiation
closed directly influences or forms one be tested using the methods described has been accepted as either 280’or 290
of the bases for the agency’s decision on in this document. The agency intends to nm. Given that the comment did not
a matter in an OTC drug rulemaking propose modified, test procedures in a provide a compelling reason to change
proceeding. the agency adds it to the future issue of the Federal Register and the proposed definition of UVB
administrative record without any necessary retesting time will be radiation. the agency will continue to
27668 Federal Register/ Vol. 64. No. 98 /Friday. May 21. 1999 /Rules and Regulations

define the boundaries of UVB radiation 7). but none were subsequently 5 1 of this document) may help to
as 290 to 320 nm. provided. The agency is not currently prevent skin damage and may help
4. Comments requested the agency to aware of stability problems that would reduce the risk of skin lesions. skin
amend the definition of a sunscreen require expiration dating for OTC cancer. and other disease conditions.
active ingredient in proposed 5 352.3(c) sunscreen drug products but wilt Products that are marketed to achieve
to include mechanisms other than address such a requirement if data these important health benefits meet the
absorption. to expand the UV range to become available. All sunscreen active definition of a drug under section
include UVA radiation. and to provide ingredients included in the final 201@(l)(B) and (43u(l)(C)of the act.
a minimum SPF value requirement. The monograph also have a USP monograph 9. One comment disagreed with the
comments added that some proposed that contains packaging and storage agency’s tentative con&sion that ~--
Category I active ingredients (e.g., reauirements and standards for omducts products containing a sunscreen
menthyl anthranilate and titanium coitaining these ingredients. ’ ingredient. but labeled for the purpose
dioxide) do not meet the proposed 7. Comments recommended that the of obtaining an “even tan,” are subject
definition, and that the definition is not agency establish procedures for to regulation as drugs. According to,the
interpretable without specifications for ensuring batch-to-batch SPF test results, comment. such a product is subject to
meas.u&ng 85 percent absorbance. and that it approve testing laboratories regulation as a drug only if it bears a
The agency discussed the need to and regulate their performance. claim to treat or prevent sunburn. The
modify the definition in a 1996 Regulations already exist to assure omment asserts that this has been the
pioposed amendment of the tentative that each batch of drug product meets agency’s consistent approach since .
final monograph (61 FR 48645 at established specifications for the 1940. . _ _.
48646). The agency agre tiiat identitv and streneth of each active Another comment stated that sunless .
modifications should.be to: (1) Include ing&d&. Spec&caliy. 21 CFR 211.160 tanning products, used to impart color
mechanismsother than absorption, (2) requires that product specii?cations and without exposui-e to the sti. could be
redefine wavelengths, and (3) remove laboratory controls be established and improved by adding a sun+i-een to’
the percent absorbance requirement. performed. Although the agency would provide users protection during&e&
The agency does fiat agree th6t a iiot require SW testing on hutian normal outside activities. The comment ” ’ .
minimum SPF value should be included sub&& for every batch produced. requested that such products should be
in the definition because thii manufacturers need to assure regardedascosmetics. because they . .
information is more appropriately a conformance to their fInished product. would be used primarily for a cosmetic :
characteristic of the final formulation. sp&ifications. Further, any changes to effect, with the suns-n protection
Therefore, the agency has revised the batch formula would. at a minimum, serving snly a’secondarypurpose.
proposed 5 352.3(cj in this document, to require review and documentation by The agency thoroughly disctissedthe
read: “Sunscreen. act+ inpdjennr An the manufacturer’s quality control unit. regulatory status of~“tanning*’ pmductsl’ .
ingredient listed in § 352.10 that, to determine if SPF.xet&ing is. including the basis for withcira&ng its
absorbs. reflects, or scatters radiation in necessary. Finally, 21 CFR211.180 l940 advisory opinion on sunburn vd .
the ultraviolet range at-wavelengths of provides for the inspection of records suntan prepatitions; in *e’tentative .
290 to 400 tianometerzi’ pertaining t0 production, control, and final monograph (58 FR 28194 at-28203
5. One comment recommended that . distribution of batches of drub products. to.28207.28293 to 28294). As .discussed
the agency reevaluate state.ments in the Thus, testing laboratories are subject to in the tentative fti.monog&ph the
‘tentative final monograph on the these regulations. .presence of a sunscreen active
harmful nature of tanning. The-agency ingredient, in conjunction with labeling ; ’
discwed.the harmful effects of UV B.. Cornmen& on the DrugXo~m&ic claims that the product may be use+;
radiation-induced tanning in t+e St&us of Stinscreen Products e.g.. to permit tanning or to acquire an
tentative final monograph (58 FR 28194 8. One comment q&stion@ whether even tan, generally establishes that the
at 28238 to 28239). The com,me,nt : sunscreen products should be regulited product’s intended use is that of a drug.
suggested that,anatural tan reduces as drugs. The comment asserted that Such pmducts suggest, among other
cumfilatlve sun exposure and may such products are not active in the things, that the ingredients in the
potentiate sunscreen effectiveness. The mitigation or elimination of a.disease product will allow the consumer to stay -
comment did not. however, provide condition, and that sunscreen p,mducts in the sun longer without suffering skin
data or references to support this cLai& have no more aff& on the structure and damage (58 FR 28294 at 28204).
or to otherwise cause the agency to function of the body than “being in Likewise, products that claim to’
than e its position. physical shade.” accelerate or stimulate the tanning
6. 8 ne comment requested that the The basis for the agency’s process are claiming, either expressly or
final mon&raph require expiration determination that prod&s intended impliedly. to stimulate the ~~O&.IC~~OKI
dating and storage information in .the for use as sunscreens are subject to of melanin in the body. Such a claim to
labeling of OTC sunscreen drug regulation as drugs under section affect the structure or function of the
products. The comment noted that 20 1(g)(1) of the Fed&al Food, Drug, and body renders the product subjea to
under 21 CFR 211.137. OTC drug Cosmetic Act (the act) .(2 1 U.S.C. regulation as a drug under s&ion
. products with data demonstrating 32 1(gp(1)) is set forth at length in the 201 (s) (1) of the act (see 58 FR 28194 at
stability for 3 years and without labeled tentative final.monograph (58 FR 28 194 28293). Finally. a sunless tanning
dosage limitations are not required to at 28203 to 28206). Essentially, product that contains a sunscreen
include an expiration date in their sunscreen active ingredients affect the ingredient, to provide protection to the
labeling. The cornmerit stated that it was strudture and function of the body by ‘consumer. is subject to regulation as a
aware of numerous cases that suggest absorbing. reflecting, or scattering the drug. The idea that the sunburn
these products rtiay not be stable for 3 harmful, burning rays of the sun. protection offered by the product may
years. thereby altering the normal only be a “secondary” feature for the
The agency requested the comment to physiological response to solar consumer is not relevant. If an intended
provide data and information about the radiation. Proper use of sunscreen use of the product is to provide users
specific products it was aware of (Ref. ingredients (see section ILL. comment with sun protection when they go
Pederal Register/ Vol. 64, No. 98 /Friday, May 21. 1999 /Rules and Regulations 27669
outside (as the comment suggests), then you don’t burn.” The comment tihe product does not provide such
the product is subject’to regulation as a concluded that the availability of I:lrotection. are sufficiently serious to
drug. tanning products without a protective require the type of disclosure outlined
‘On the other hand, products that do sunscreen ingredient is a serious health n the proposed rule. information about
not make express or implied sun issue and detrimental to public health. he purpose of a sunscreen ingredient in
protection claims. and do not contain A third comment objected to any such aI hair care or nail product wit1 be useful
sunscreen ingredients, may be regarded warnings on tanning products. to consumers to inform them that the
as cosmetics under section 20 1(i) of the The agency considers it an important ngredient protects only the hair or only
act. If the product is intended solely to public tiealth issue that users of t he color of the product.
provide cosmetic effects on the skin suntanning products be alerted when This information need appear only
(e.g.. to moisturize the skin while these products do not contain a ,nce and can appear anywhere in the
sunbathing). or solely to impart color to sunscreen and do not protect against .abeling. provided the qualifying
the skin without exposure to the sun or sunburn or other harmful effects to the 3urpose appears prominently and
other sources of light (i.e., sunless skin. Because suntanning products are :onspicuously and in conjunction with
tanning), then the product may be intended for repeated use under the sun :he word “sunscreen.” The information
marketed as a cosmetic. Such products, or suntanning lamps while acquiring’s may. e.g.. be combined in a single
however, must include a warning . tan, the agency considers failure to . statement, e.g., “Gmtains a sunscreen-
statement (discussed in this section, provide information on hazards to protect product color.” This will
comment 10 of this document) to inform associated with repeated. unprotected ensure that consumers will see and
the co’nsumer that the product does not exposure to UV radiation to be a failure readily associate the two pieces of
provide any protection against sunburn. to reveal material facts (see sections information.
Products marketed to enhance or permit 261(nj.‘502(a), and602(a) of the act (21 12, Two comments objected to the use ~ ,
tanning that do not contain a sunscreen U.SC. 352(a) and 362(a))), especially in of an OTC drug rulemaking.process to ..
ingredient must be reviewed on a case- light of. the representations that are change-cosmetic labeling require@r~ts. .
by-case basis to determine whether the made for the product (e.g., suntanning). i.e.. the addition of a warning on certain
product is intended solely to provide a Therefore. the agency is requiring the tanning products and the labeling .’
cosmetic benefit (such as ~moistu?izing) labeling of suntanning preparations that requirements for hair care or nail
or whether the product is intended to do not contain a su nscreen ingredient products that contain a sunscreen.for a. . : .
enhance or permit tanning by some (§740;19 (21CFR740.19)) to bear the nontherapeuticuse. ..
-other mechanism of action. following: “WamingTThis product The agency addressed thii procedural
The comments offered no other does not contain a sunscreen and .does concern. which was also raised in
reasoning and no data t;p the contrary, not protect against sunburn. Repeated response tothe ANPRM. at length in the
other than to suggest *at the agency’s exposure of unprotected skin while . tentative final monograph. (58 FR 28 1Y4
approach would encourage tanning niay.inc&se the risk of skin at 2820 1 to 28202). The industry and
manufacturers to remove sunscreen aging, skin cancer. and other harmful consumers have had ample notice of the
ingredients from suntan products.and. effects to the skin even if you do not fact that this proceeding included
thereby. expose conSumex% to even bum.” The agency considers this several cosmetic labeling issues that.
Mgher levels of harmful ultraviolet iays. information to be sufficiently important, arise out of the same facts and findings
The agency is not persuaded that a for safetv reason&. to reouire.a 1Zmonth at issue in developing the OTC drug
significant number of manufacturers effective’ date .(asbppos&i to 24 months. monograph. It is not uncommon fo@he.
will choose to reformulate their for .the balance of the rule) and to agency to address in an OTC nilemaking
products, to make them less safe for require the strongest possible signal document the sta&rs of, or the regu@titin
consumers. as a result of this final rule. word, i.e..‘“Waming.” of. products that fall outside of the
Moreover, consumers will continue to 11. One comment disagreed with the monograph. In this instance, the.
have an array of sunscreen-containing proposal that hair care and nail cosmetic labeling issues were so closely‘
products from which to choose. Finally, products that contain a sunscreen related to the OTC drug issues thatra
as discussed below, certain tanning ingredient for a nontherapeutic use (e.g.. separate proceeding would have been
products (including sunless tanning to protect the color of the product) ; and overly duplicative and inefftcient.’
products) that do not eontain sunscreen that use the term “sunscreen” in’the .
ingredients must bear a prominent labeling. must describe in the labeling C. Comments On S&cific .Suns&n
warning to the consumer. This will the functional role of the sunscreen. Active’lngredients
ensure that the consumer is fully According to the comment, it is highly 13. Severalcomments notedthat FDA
informed as to which products offer sun unlikely that consumers would think had deferred a decision on the citizen
protection and which do not. that these products are intended to petitions requesting that sunscreen
10. One comment requested that the protect the skin. If this requirement active ingredients marketed solely in
signal word “Caution” replace the were finalized, the comment requested foreign countries be included in the
signal word “Warning” preceding the that the agency permit the term : OTC sunscreen monograph. The
following statement for suntanning “sunscreen” to appear once anywhere comments urged FDA answer these
preparations: “Warning-This product in the labeling, with the purpose of the petitions and establish a policy
does not contain a sunscreen and does sunscreen explained elsewhere in the concerning the inclusion of OTC
not protect against sunburn.” The labeling. sunscreens based solely on foreign data
comment stated that the word The agency disagrees with the and marketing experience.
“Warning” suggests safety hazards premise of this comment: The use of the In the Federal Register of October 3.
associated with these products that are term~“sunscreen” in labeling suggests 1996 (61 FR 51625)rthe agency
unrelated to sunburn. Another comment that the product in some way will published an ANPRM that addressed
petitioned to add a second sentence to protect the consumer from the harmful establishing eligibility criteria for
the warning: “Tanning in sunlight or effects of the sun. The health risks considering additional OTC conditions
under tanning lamps can cause skin associated with relying on a pkoduct for (i.e., OTC drug active ingredients.
cancer and premature skin aging-even if protection from thesun. when in fact indications. dosage forms. dosage
,
:
. ; :

strengths. routes of administration, and developed or adopted need not be has an allergy to aminobenzoic acid. the
active ingredient combinations) in the resolved in this proceeding at this time. individual may suffer adverse health
OTC drug monograph system. These Similarly. TEA and DEA need not be consequences.
proposed criteria would address how addressed in this proceeding. as For these reasons. and especially in
foreign or domestic OTC marketing triethanolamine is not a sunscreen light of the potential safety concerns for
experience could be used to support the active ingredient. and diethanolamine is certain consumers. the agency
inclusion of an ingredient in an OTC only used in the ingredient concludes that wherever the ingredient
drug monograph. Specifically, the diethanolamine methoxycinnamate aminobenzoic acid appears in the
criteria would address how OTC which. as discussed. is not a monograph labeling of an OTC sunscreen drue
marketing experience in the United ingredient at this time. . product. including labeling that &es
States or abroad could be used to meet. With respect to the comment on the the absence of this ingredient. the
the statutory requirement under section monograph ingredient descriptive term PABL must
201 (p) of the act of marketing “to a phenylbenzimidazole sulfonic acid. the immediately follow the established
material extent” tind “for a material agency agrees that if USAN or the USP name; i.e.. “Aminobenwic acid
time.“, “ Material extent” and “material were to adopt a different or altematlve (PABA).” Thus, e.g., a’ product that is
time”. are needed to quaIffy a specific name for this ingredient, such a name’ currently marketed as “PABA-free” .
OTC drug condition for consideration could be used in the labeling of a .. would now be required to state that the.
under the OTC drug monograph system. product that contains this ingredient; As product is “Aminobenzoic acid (PABA)-
The decision on whether to proceed dlscussed in comment 30 of the .,he.” This convention will allow .
with a final rulemaking on this subject tentative final monograph (58 FR 28194 consumers to begin to recognize that the
will be based, in part. on the at 28207to.28209). the agency is using ingredient they may wish to avoid is
informrition and comments submitted in the conipendial name as the established ‘Yaniinobenwic acid.” After .a.sufticient
response to. the notice of proposed name for each active ingredient. period of time, the agency will revisit
rulemaking that the agency is preparing 15. Two comments mouested that the the need for consumer Tabellng’tis”‘” . --” ‘:’
for publication~in a future issue.of the term.“PABA” continue tb be allowed in continue to bear the descriptive term
Federal Register. Resolution of the labeling. The comments stated that the PABA. .
pending su~nscfeen petitions-must aw’ait nameaminobenzoic acid.is meaningless 16. One comment s&ted that claims of
the outcome of any final rulemaking on to consumers and physicians, who over protection by artificial melanin. ,
this subject. the years have learned to recognize this melanin-containing products, and
14. One comment requested that the ingredient on the label as PABA. One antioxidants should be enumerated. .
agency tidopt simpler, more user- comment recommended the use of. well regulated; .and defined.
friendly, names for several sunscreen aminobenzoic acid in the Ingredient list -The agency agrees v&h the comment.
ingredients: (1) Roxadlmate for ethyl- and the’use of PABA in other but these claii are not cover6d.b~ this
[bis(hydroxypropyl)] &ninobenzoate. (2) communications a*Jt .the product, The final monograph. Melanin and artificial _
lisadimate for glyceryl aminobenzoate. comment added that the term “PABA- melanins are not recognized sunscreen
and (3) diolamine methoxycinnamate free”-should be aliowed on products active ingredients. Any p@duct
for diethanolamine methoxycinnamate. that do not-contain aminobenzoic acid. containing melanin or artificial
The comment claimed that these names The other comment proposed either to melaninsas active ingredients and
had been adopted or designated by the permit the listing of the ingredient as making sun protection claims would
United States Adopted-Names (USAN) PABA or:if that is unacceptable, as have to seek marketing approval under.
Council. The comment also requested PABA (aminobenzoic acid): a new drug application @IDA).
that if USAN adopts a name for In comment 30 of the tentative final The agency is aware that claims of
phenylbenzimidazole sulfonic acid, monograph@8 FR 28194 at 28207 to protection from antioxidants are used in
FDA adoptthisn&neaswell. The 28299). the agency dis&sed the Issue the labeling of some cosmetic products
comment .also suggested the .use of the of .the appropriate established name for. with or without a sunscreen. The agency
acronyms ‘TEA” and “DEA” for this and other ‘sunscreen ingredients. As will ascertain the nature of any such
Methanolamine and diethanolamine. the agency stated in that discussion, ‘the claims (drug or cosmetic)‘on a case-by-
recognized compendia1 name for easebasis.
?!?lggE%y is including in this final aminobenzoic acid no.longer includes’ .17. Several comments objected to the I
monograph only those active the term PABA. agency’s proposal that OTC suns6reen~
ingredients that are the subject of an The agency acknowledges:however. drug products must contain less than
official USP compendia1 monograph that the term PABA formerly was part 500 parts per billion (ppb) of Nimethyl-
that sets forth its standards of identity, of the established name for thii N-nitrosoaminobenwat~ octyl eSter
strength, qdality. and purity (see section ingredient and that the t&e of the term (NMPABAO) for several.reasons: (1)
I of this document). In the Federal in consumer labeling has continued Toxicological studies indicate that
Register of June 8. 1994. FDA deleted despite the change in the compendia1 NMPABAO does not have mutagenic or
ethyl-[bis(hydroxypropyl)] name. In addition, the agency agrees .suspecteci carcinogenic potential (Ref.
aminobenzoate and glyceryl with the comment that many consumers 8). (2) NMPABAO may be present in .
aminobenzoate from the tentative final have learned to recognize this . sunscreens containing padimate 0 only.
monograph due to the lack of interest in ingredient as, and only as, PABA. The in small amounts (ppb range) and the
establishing USP monographs for these agency also recognizes that consumers risks associated with NMPABAO are
ingredients. Moreover, two sunscreen seeking to avoid the use of this very low, (3) NMPABAO decomposes
ingredients (including diethanolamine ingredient for health-related reasons quickly when exposed to UV radiation.
methoxycinnamate) have been deferred (e.g.. allergy) may. in this case. be and (4) industry is aware not to
from the final monograph due to the misled if the- term PABA. were no longer formulate with known nitrosating agents
lack of a current or proposed permitted. Some consumers may believe in the presence of amines in order to :
compendia1 monograph. Therefore, the that a product that lists aminobenzoic avoid nitrosamine ‘contamination’of its
issue of whether a “user-friendly” name acid as an ingredient. but does not list products. Some comments stated that
for these ingredients should be PABA. is PABA-free. If such a consumer FDA’s own conclusions in the tentative
Federal Register/ Vol. 64. No. 98 f Friday. May 21. 1999 /Rules and
^. Regulations 27671
final monograph concerning the safety submitted to the Toxic Substance he skin. The comments added that
of both NMPABAO an‘d padimate 0 do Control Act 8(e) coordinator of the nicronized titanium dioxide meets all
not support the imposition of United States Environmental Protection ;afety and efficacy criteria and also
concentration limits for NMPABAO in Agency for consideration. The study neets the USP specifications for purity
sunscreens nor do they justify the high was a $-week repeated dose study at except pure water content.
cost of analyzing each batch of doses of 0, 100.300. and 1.000 Another comment asserted for the
sunscreen product for NMPABAO. One milligrams (mg)/kilogram (kg)/day of Tollowing reasons that micronized
comment contended that any proposed padimate 0 administered by gavage in :itanium dioxide is a new ingredient
limit should apply to all nitrosamines a corn oil vehicle (10 to 15 rats/group/ Nith several unresolved safety and
and not just NMPABAO. The comment sex). The study included a 4-week efficacy issues: (1) It does not meet the
stated that nitrosamines can be formed recovery period to assessthe persistence definition qf a sunscreen opaque
from any secondary or tertiary amine. or reversibility of any toxic effects. At sunblock, (2) there ls no control of
Several sunscreen active ingredients the end of the 4-week treatment period, particles to agglomerate. which ls
contain this moiety in their chemical toxic effects were seen in four target critical to effectiveness, (3) no standards
structufe and many inactive ingredients organs: Testes, epididymis. spleen, and exist to ensure integrity of coatl~gs. (4)
are secondary or tertiary’amines. The liver. The no-observed-effect-level in there are no performance-based
comment concluded that targeting this study %%s100 mg/kg/daj for both standards of identity: micronized
NMPABAO falsely conveys that’ males and females. Toxic effects titanium dioxlde’ls not included in the
padimate 0 is a unique concern. appeared reversible in the animals USP. (5) 15 phdiocatalyst potential. and
resultiilg in manufacturers using other necropsied after the 4-week recovery (6) the potential for the smaller partlclq
ingredients to avoid costly testing and period with theexception of marked size to accumula& tinder the skin. .
ne ative impllcatio*. &pidldy&l hypospermia.at the. l.Oqd The agency finds the.data with the
is the tentative final.monograph. the m kg/day dose (5/5 animals): . comments Supportive of motigraph .
agency did not propose a conCentratlori %I e clixiical relevance of this animal status for micronized fitanium,di&lde. . “.
limit on NMPABAO. Rather, based on toxicity study is difficult t0 ‘Guess. Acute animal toxicity, izritatiun. .
Concerns that had been raised, the . Padimate 0 was admlnlltered . Sensitization. photoirrltation, . ’
agency asked for comment on whether chronically and at very high oral dbses. photosetiitlzation. and human repeat -
it should consider proposing a fuced’ Under normal use conditions. sunscreen
limit. As discussed in’& tentative final insult patch Bnd skin penetration
drug products containing padllte 0 studies revealed nodeleterious effects. . = ”
monograph (58 FR 28194 tit 28288 to are applled topically and used SPF values for four prod&t
28293). toxicological studies Support the intermlttently. In addition,
agency’s belief that the risk associated pharmacokinetlc.pa -tiere not formulations contairiing from 4.4 to. 10
with NMPABAO contarinination of calculated and the different routes of percent’ inicronizeci’ tltaniti d&tide
sunscreen drug prod&s .is very low due administration (oral in this study versus were from 9 to 24’and support ..
to NMPABAO’s low:mutagenlci!$ imd ‘topical for sunscmen ~IXK&X&) preclude effectiven&s F a suns*? higredli?nt;
carcinogenic&y potential and rapid calculation of a “safety margin“ on the The agency is .aware that sunscreen
decomposition in the presence of UV basis of dose per unit of body weight or manufacturers are using xiilcronlzed
tadiation. The agency has not become surface area. Similarly. kinetic data a&~ titanium dioxide to create high SPF
awake of atiy new data or infoimation not available for a comparison of serum products that are transpqnt,and .,
since the publication of the tentative levels of &ug or metabolltes. Literature esthetically pleasing on the skin. The
final monograph suggesting a safety searches indicate no published agency does not consider micronized
concern with NMPABAO in sunscreeii information on the klnetlcs of padimate titanlum.dloxlde to be a new ingredient
drug products. Therefore, ‘the agency 0 wi* topical application in man. If but considers it a specific grade of the
has decided not to propose or dtheruiise petitaneous absorptiori’of padimate 0 titanium dioxide originally reviewed by : _
include in this final monograph a . does occur in man, it se‘eins likely that the Panel. Fairhurst and Mitchnick (Ref.
requirement that OTC sunscre& drug. @e peak and/ot’cumulative levels 11) note that “fines” have m.part of
prod&s must contain’less than 500 ppb -achieved with sunscreen usage would comme+alIy tied titanium dloxlde
‘r df NMPABAO. be Quita low compared to the systemic’ powders for decades, and that a
In the tentati+e final monograph (58 exposure achieved in this animal . micronized product simply refers to’s :
FR 28194 at 28292). the ag$ncy toxicity swdy. Further, it is not known refinement of particle siie dlstrlbutlon:
discussed its analysis for NMPABAO in whether the irreversible epididymal .. E+sed ondata and information
25 commercially available sunscreen hypospermia found in the 1.OOOtig/kg/ presented at the September 19 tid 20.
products. Of the 11 samples found td be day group would also be reversible with 1996. public meeting on the
contaminated with NMPABAO. the four more time. photobiology and photochemistry of
highest contained 2-bromo-2-nitro-1,3- .’ The agency has determined that thl& sunscreens (Ref. 12). the agency ls not.
propanediol. an indirect nitrosating study dqes not present sufficient data to aware of any evidence at this t@ne that.
agent. The agency concluded that there exclude ‘padimate 0 from the final demonstrates a safely concern from the
would be ,no nitrosamine contamination monograph and that an adequate safety use of micronized tltanium dloxlde in :
if these products were formulated margin exists for its .use as an OTC sunscreen products. While micronized
without the nitrosating agent. As noted sunscreen ingredient. titanium dioxide does not meet the .
by several of the comments, the industry 19. Two comments submitted safety proposed definiti0.n of a sunscreen
is aware not to formulate with known andfor efficacy data to support Category opaque sunblock, the agencyhas not
nitrosating agents in the presence! of I status for micronized titzinium dioxide included the use of this t&n in the final.
amines in order to avciid nltrosamine (Refs. 9 and 10). One comment stated .monograph (see section ILL. comment.
contamination of its products. that micronized titanium dioxide is not 52 of this document). The potential for
18. One comment submitted a a ,new material but Is a selected . titanium dioxide particles to
reference to a subchronic oral toxic&y distribution of existing material that agglomerate in formulation. which
study in rats conducted with padimate provides higher SPF values while being could result in lower SPF values. is
0 which a chemical manufacturer had transparent and esthetically pleasing on addressed by the final product SPF test.
27672 Federal Register/ Vol. 64, No. 98/Friday. May 2 1. 1999 /Rules and Regulations

The SPF data that the agency reviewed ingredients when used in combination. Although the agency needs assurance
(Ref. 9) did not indicate such a problem. One comment (Ref. i5j submitted in tliat each ingredient is contributing to
Micronized titanium dioxide meets vitro SPF testing data for several the effectiveness of the product. it does
current USP monograph specifications different combinations. Although these not want to impose unnecessary testing
for titanium dioxide wit.h the exception data showed a statistically significant requirements on sunscreen product
that the material contains more increased efficacy for lower than manufacturers. Therefore. the agency is
associated water. In both the July minimum concentrations, they were not removing the minimum concentration
through August 1996 and 1998 issues of predictive of the SPF values that would requirement for sunscreen active
the Pharmacopeial Forum (Refs. 13 and be obtained with human testing and. ingredients proposed in S 352.20 and is
14). the United States Pharmacopeial therefore. were not used to support adding the requirement that: (I) The
Convention published in-process lower concentrations of sunscreen concentration of each active sunscreen
revision proposals to make the active ingredients when used in ingredient used in a combination
monograph for titanium dioxide more combination. The other comment (Ref. product must be sufficient to cont.&&
applicable to ingredients used in 16) submitted in vivo SPF testing data a minimum SPF of not less than 2 to the
sunscreen drug products. The agency conducted according to the procedure finished product. and (2) the finished
will work with the USP in the future to proposed in the tentative final product must have a minimum SPP of
update this monograph as necessary. monograph (58 PR 28194 at 28298 td notlessthanthenumberofthe ‘. ..
20. One comment stated that it is 28301) inwhich a selected cross section sunscreen actiire ingredientsused in
unnecessary to set the makimum limit of active ingredients -were tested in pairs combination multiplied by 2. .
of titanium dioxide at 25 ,percent. by substituting water or the solvent
The Panel discussed the safety and E. Comments on Labelitig and Testing ’
.system for theactive ingredients. The P,roceduris for WA Sunscreen Di-tig . ...
effectiveness of 2 to 25 percent titanium data were evaluated using a matched .-:.- i
dioxide inthe ANPRM (43 FR 38206 at Products . :
pairs comparison statistical hyPothe.sis
38250) and the agency concurred with test procedure and demonstrated that 22. In thesunscreen tentative final
the Panel’s findings in the tentative final concentrations ofsunscreen active monograph (58.FR 28194 at 28232 and .I..
monograph (58,FR 28-194 at 28295). The ingredienti lower than the minimum 28233). the agency proposed to allow - .
comment submitted no data and-the concentrations proposed in claims relating to. “broad spectrum . . ..
agency has no data to support the use S 352.20(a) (2) for combination products protection” or “UVA radiation .. .
of titanium dioxide in’sunscreen drug can provide protection” for sunscree nproductsz (I)- _.
products at concentrations higher than - I_ a significant contribution to Containing sunscreen~active ingredients
^- . product &hXttveness.
ZS percent. The agency recognizes that with abso$tion spectra extendkgto -’
D. Cornmerits on Dos&es for Sunscreen technological advances in sunscreen 360 nm or above:and (2) that
formulation technology since 1978 have demonstrate mean!ngfG WAradiation . .-
Drug Products ‘. .,’
resulted in the ability. to formulate protection &ing appropriate testings
il. Several comments objected to the products w&h lower concentrations of procedures to be developed. The agency . .
minimum~concentr%tion.req~uirements active ingredients and higher SPF received numerous comments
for sunscreen active ingredients when values. The agency also recognizes that concerning such claims and current .
used in combination because they: (1) .
final‘product testing.-and not the scientific evidence implicates UVA
Are a less effective measurement of concentration of the active ingredients radiation a$ a major cause of. among
effectiveness than a performance.based in the combination..ensures product other things, photoaging of the skin
SPF test, (2) impact on creativity and effectiveness. (Refs. 17 through 20).
innovation of new formulations Due to the recent advances in ‘. In the Federal Register of September .’ .. _ .I
(technological advances since sunscreen formulation and the data 16. 1996. and October 22; 1998. the ... -0 .
publication of the 1978 ANPRM have referenced previously, the agency is agency proposed aspecific skin damage
resultedIn higher SPF valuesusing concerned that setting minimum and premature skin aging claim for .* . .-
lower concentrations of active concentration requirements for active sunscreen products containing sptkiflc
inmients) , (3) increase potential for ingredients in sunscreen combination concentrations of avobenzone oizinc .
irritation and allergic reactions due to drug products mild subject consumers oxide basedupon the submission of
unnecessarily high concentration levels to unnecessary levels of active data to support claims of WA radiation. ..
of active ingredients, (4) contradict ingredients. Therefore, the agency is protection in such products. The agency .. .
FDA’s position that the lowest effective only requiring the maximum Will address comments-pertaining to
dose of an active ingredient be used to concentration limits in 5 352.10 for measurement of UVA radiation
produce the desired treatment effect, (5) sunscreen active ingredients when used protection in sunscreen products and
result in higher manufacturing and in combination with another sunscreen related UVA radiation protection claims
consumer costs due to unnecessary or when the combination is used with in a future issue of the. Federal Register.
levels of active ingredients, and (6) any other permitted active ingredient. Until then. WA labeling may continue
affect international harmonization .However. any such ingredient used in in accord with the tentative flnal ‘.
because Canada. Australia, and the combination with one or more monograph, and its amendments.
European Union have no concentration sunscreen active ingredients must be
minimums for active ingredients when consistent with the regulations in F. General Comtients on the Labeling of
used in combination. 5 33O.lO(a)(4)(iv). i.e., each of the Sunscreen Drug Products
One comment petitioned the agency combined active ingredients must make 23. Several comments requested that
to amend proposed S 352.20 of the a contribution to the claimed effect. the products containing sunscreen . .
tentative final monograph to include a combining of active ingredients must <ingredients as an adJunct to their main I ‘.
provlsion for formulating combination not.decrease the safety or effectiveness purpose.(e.g.. a daily moisturizer or a
sunscreen products at lower minimum of any. individual active ingredient. and lipstick with a sunscreen) be considered
concentrations._- Two comments the combination must provide _rational “secondary sunscreens” (intended only
submitted efficacy data to support lower concurrent therapy for a significant _ for incidental or casual sun exposure)..
concentrations of sunscreen‘active proportion of the target population. and should be subject to’dtfferent
Federal Register/Vol. 64. No. %/Friday, May 21. 1999 /Rules and Regulations 27673
--
labeling requirements’from “primary” 30 or higher to provide adequate language in the labeling to suggest or
sunscreen products. A number of protection. whether for continuous imply an unapproved therapeutic or
comments likewise contended that some beach exposure or everyday (incidental) physiologic effect. would likely be
of the !abeling requirements for “beach” sun exposure. subject to regulatory action as an
or “primary” sunscreen products are not The agency agrees that all sunscreen unapproved new drug (58 FR 28194 at
appropriate for “non-beach” or products (whether drug only or drug- 28286 to 28287: see comments 37 and
“secondary” sunscreen products. cosmetic) should be held to the same 38 in section II.1 of this document).
For example, the comments stated standards (e.g.. active ingredient(s). 25. Three comments contended that
that neither the proposed testing requirements, and labeling). the terms “natural.” “non-chemical.”
“Recommended Sunscreen Product Regardless of what type of product a and “chemical free” are false and
Guide” nor any other references to consumer chooses for sun protection, misleading in the labeling of OTC
sunburn or sunburn protection should the essential information relevant to sun sunscreen drug products. The commenrs
be required for secondary sunscreens. protection is the same. Thus. to ensure requested the agency to restrict the use
Some suggested that the warnings be that consumers are adequately protected of these terms. especially for sunscreen
reduced for secondary sunscreens to a from overexposure to the sun, all products containing titanium dioxide
statement such as “For external use products intended for useas sunscreens and zinc oxide.
only. keep out of eyes. Discontinue use should have similar labeling . Generally. the appropriateness of .
if signs of irritation appear.” One requirements. irrespective of their these terms requires casa-s-c
comment recommended that the method .of use and irrespective of . analysis to determine whether their use
statement of identity fora secondary whether the sunscreen use is considered would render the product false or
sunscreen should be its dsmetic primary or secondary to the product. misleading in any particular (see
function, e.g., “moisturiaer~~’ Ahother Consistent with this approach. the sections 502(a) and 602(a)ofthe,aaj.
recommended stating the primary agency has developed uniform. . . The agency notes, however. that the use
(cosmetiti) function first, then the streamlined labeling for all sunscreen of.the terms “non-chemical” and
secondary (drug) function, e.g., products (seesections II.1 through II+. of “chemical~free” in the labeling of an
“moisturizing face cream with this document). . OTC’sunscreen drug product, to
sunscreen (or with SPF - The agency also notes, however, that describe the ingredients contained in ’
sunscreen) .” a number of the labelingissues raised in the product. is likely to be considered .
The comments also suggested that these comments. including the issue of unacceptable. Sunscreen drug products .
secondary products be permitted to bear the “Recommended Sunscreen Product contain active (and often inactive)
certain labeling claims relating to aging, Guide,” are addressed elsewhere in this ingredients that have been obtained
such as “I-Ielps reduce the chance of document. In addressing these issues. through a chemical process. orthathave
skin aging caused by ir$idental (or the agency gave careful consideration to been formulated into the finished
casual) exposure to the sun.? or *‘Helps the wide variety of ‘products marketed product through a chemical process.
reduce premature aging from incidental for sunscreen uses. . The term “natural” is more likely to
(or casual) exposure to the sun.” Some Finally. the agency notes that under require context-specific analysis
also requested the option of being the recently issued standardized OTC particularly when used in Iabellng to
allowed to relate skin aging claims drug product labeling format (§ 201.66 describe certain cosmetic aspects or
directly to sun exposure, to inform (2 1 CFR 20 1.66)). manufactun& will uses of a sunscreen pro&cL The term
consumers more clearly that sun not be allowed to commingle drug and . “natural.” however. would not be
protection isnot the primary attribute.of cosmetic claims within the “Drug Facts” permitted to appear within’ the requi.r&I .
the product, e.g.. “Provides moisture to portionofthelabeling. - OTC drug labeling of a sunscreen
facial skin throughout the dav while 24. One comment requested product and is not considered to be
protecting facial&n from skin aging clarification of the age&y’s discussion interchangeable with any of the final
due to &o&e to sun.” Other of the term “anti-aging” as a claim or as sunscreen monograph Language.
cornmen& recommended that the part of a trade name (58 FR 28 194 at 26. Four commenk oonosed anv’
proposed “Sun alert+’ statement or other 28287). The comment was concerned labeling that a suns&produti”does
references to “skin cancer” or other that products containing no sunscreen not provide UVA protection.”
cancers should not be required for active ingredients and no sunscreen contending that FDA’s policy does not
secondary products. claims, but which are sold under’“anti- require disclaimers of broaderpurposes
On the other hand. the agency also aging” trade names, would be subJect to for which products are not useful. One
received comments opposing the idea of regulation under the OTC drug comment added that an SPF 15 produd
recognizing “primary” and “secondary” sunscreen monograph. must blockUVAradiatioti to.be .
or “beach” and “non-beach categories The use of “anti-aging” language in a effective in preventing sunburn.
of sunscreen products. One comment prqduct ‘that made no sunscreen claims Two comments argued that a
. stated that any product containing a and contained no sunscreen active “negative.waming” would be useful d
sunscreen for the purpose of protection ingredients .would not. as the comment necessary to warn and protect
from the sun’s harmful effects should be asked, cause the product to fall within. consumers and suggested “Does not
held to the same standards as other the scope of the OTC sunscreen drug provide bmad spectrum WA
sunscreen products. Another comment monograph. Such a product may, protection.” or ‘Caution: This product
disagreed with the idea of allowing however, be subJect to regulation as a does not provide protection from the
different sets of claims for “primary” drug and as a new drug. under section recognized dangers of UVA rays which
and “secondary” products. According to 201(g)(l)and(p)oftheact,orasa may contribute to skin cancer and other
this comment, claimssuch as “Helps cosmetic under section 20 1(i), or as both chronic skin disease.”
reduce the chance of skin aging” are a drug and a cosmetic. depending upon Labeling should primarily direct
drug claims and should be regulated as all of the circumstances surrounding its consumers towards the purposes for
such. Finally, one comment stated that distribution. A product that is marketed which a product is considered useful
any sunscreen product (primary or under the flnal OTC sunscreen drug However, in establishing the conditions
secondary) must have anSPF of 15 to monograph. but which uses anti-aging for the safe and effective use of an OTC
27674 Federal Reglster/Vol. 64, No. 98/Priday. May 21. 1999 /Rules and Regulations

drug product. the agency also must take agency’will consider including this type The data provided by the comments
into account, among dther things, the of professional labeling in the in support of allowing numerical values
context in w.hich a product is monograph in the future when specific above 30 were of only limited use. Data
customarily marketed and the potential supportive data are provided. from a field survey of 62 sunbathers on
that consumers may use the product for Miami’s South Beach during July 1993
a use for which it may not be beneficial G. Comments on Sunscreen Drug
(Ref. 2 1) did not provide any reliable
(see sections 20 1(n) and 502(a) of the Products With High SPF Values
conclusions on the frequency or extent
act; 5 330.10(a)(3)). 29. Numerous comments objected to of solar overexposure by light-skinned.
With these factors in mind, the agency the proposed maximum SPF value of 30 individuals or a benefit provided by
will further evaluate whether “negative for OTC sunscreen drug products. The sunscreen products with an SPF value
warnings” or disclosure statements are comments requested eitherthat the above 30 as: (1) The sample size was
needed when it completes the WA agency adopt no limit or a limit of SPF small and the survey population did,&
portion of the sunscreen monograph in 50. for the following reasons: (1) UV represent a random sample. (2) the MED
a future issue of the Federal Register. radiation exposure is increasing due to. was not determined under controlled
27. Four comments contended that both lifestyle changes and depletion of cdnditions or standardized procedure:
the signal words “Indications” and the atmospheric ozone layer,, (2) skin, and (3) full-day WB radiation exposure
“Direct.ions” are not needed, take up ..
cancer rates are increasing and there is was based on crude extrapolation of
valuable label space, and should either no safe threshold to’prevent cancer. (3) weather data.
not be required or be optional, people using an SPF 30 sunscreen will Data from MED deterrr@ations on
especially for sunscreen-containing drug have slight sunburn after receiving their 1.332 people with skin types I. II, and
products that have some”traditional” 30 MED and therefore should have III. and W radiation data. for the month
cosmetic uses (e.g.. lipsticks). available sunscreens with higher SPF of June 1974 in 5 cities in the United
The agency allows the signal word States (Ref. 22). support the c+ention
“Use’.’ or “Uses”- in place of .- .. @u.es, (4) high SPF sunscreens rire -_.._
needed for extremely sun-sensitive. . that a sizeable population may exist that
“Indication” or “Indications.” This ‘k at risk to more than 30 MED’s of W .
short signai word is useful-for .’ p-eopIe during peri.& of unavoidable,
intense or lengthy sun exposure, and radiation per day: However. the data are
consumers. appropriate for dual use insufficient for extrapolation t0 the
products, and does not clutter label because.of less than l&al usage by
consumers due to misjudging of their .general population. The small sample
space. Likewise. the agency concludes size in this study’limits thesensitivity
that the signal,word “Directions” is skin type and/or inadequate/infrequent
application, (5) there is a significant of the study and the study population
useful for consumers and does not did not represent a random sample.
clutter label space. (64 FR 13254 at . variation of skin types. sensitivities, r&d
W radiation exposures among people, Finally. data from animal studies (Ref.
13264 to 13268. March,.17. 1999). The 23) showed that: (1) Limiting sunscreen :
agency is inc1uding.s 352,52(f) in this (6) formulation techniiues can increase
‘SPF values without necess&ly protection to SPF 30 may not be p&dent
final .monograph’ to.provide labeling if UV radiation damage is not related to -.
modifications for sunscreen products. increasing ingredient concentrations, (I,
current information does not support an SPF, (2).a greater amount of sunscreen.
that meet the small package is needed to completely inhibit-some of
specifications in S 20 1.66(d) (10) and are association between.high SPF products
and safety concerns, and (8) high SPF the nonerythemogenic damage caused
labeled for use on specific small areas by UV radiation, and.(3) .’ .
of the face (e.g., lips. nose. ears. and/or products provide for greater relative nonerythemogenic effects (e.g.;
around eyes). These products include. . exposure times and decrease.d’W photoimmunosuppression) occur with f
many traditional cosmetics (e.g., lipstick radiation transmission. Three comments suberythemal doses of W radiation. (as
or eye. makeup) that may contain ’ (Refs. 21.22, and 23) submitted can be obtained with the use of low or
sunscreens. These products will be I supporting data. . high. SPF sunscreens). While the agency -
allowed to present a condensed “Uses”’ Some comments stat&I&at “High agrees that hl8her SPF values may
section and may omit directions for use SPF” (i.e., above SPF 30) products are provide for greater relative exposu?e :
if they are marketed in a lipstick form. ‘on the market and used by consumers, times, the SPF testis not the apProp&e
28. One comment requested that the ‘and that limiting SPF values would measurement of protection from
mono@ aph include professional . stifle sunscreen product development nonerythemogenic damage because SPF : :
labeling for both UVB and UVA and preventative health benefits. Other is 0nly.a measure of erythema. The’ .’
radiation protection to assist health comments argued that sunscreens with agency finds that the data from these
professionals to select appropriate high SPF values provide increased studies were not sufficient-to either
products. The comment recommended protection from ultraviolet radiation support or dismiss limiting the.
inclusion of the absorption spectrum of effects such as maximum SPF value in this final rule.
each sunscreen in the product and photoimmunosuppression and are The agency continues to agree with
suggested that the labeling include needed by those. with “dermatological the comments about overall increases in
.information that the product: (1) problems.” both W radiation exposure (58 FR
Protects against drug-induced ’ In contrast. some comments 28194 at 28223). skin cancer rates (58
photosensitization reactions induced by supported the agency’s proposal to limit FR 28194 at 28227). and the variation of
UV radiation in the ranges -rimto SPF values to 30 to stop the promotional skin types, sensitivities, and UV
nm. and (2) other truthful and “bidding war” or “horsepower race.” radiation exposures among people (58
nonmisleading statements describing Another comment contended that real FR 28 194 at 28222). Tlie agency also ..
both’UVB and UVA radiation protection cvnsumer benefit is achieired through agrees with the comment that a person
against photosensitization reactions. .appropriate balance of SPF. using an SPF 30 sunscreen could have
The agency did not propose substantivity. UVA radiation protection, a sitght sunburn after being exposed to
professional labeling in the tentative irritation potential. and cost, whereas their 30 MED (i.e.. after their skin
final monograph, but did ask for data to SPF values above 30 provide only receives a MED). However. the agency
be submitted (58 FR 28194 at 28210 and “incremental benefit” and an continues to believe that an SPF 30
28245). No data were received. The unnecessary increase in drug exposure. sunscreen product provides adequate
Federal Register/Vol. 64. No. 98/Friday. May 21. 1999 /Rules and Regulations 27673

protection for the majority of consumers will cause the product to be misbranded resistance studies (Ref. 24) utilizing
even under extreme conditions. less under section 502 of the Federal Food, methods proposed by the Panel in the
than ideal usage. or in varying weather Drug. and Cosmetic Act (the act).” ANPRM (43 FR 38206) and involving a
conditions (58 FR 28194 at 28225). Numerous comments from total of 1 17 subjects. The comment
On the other hand, the agency is also dermatologists asked that a specific SPF concluded that the water resistance t-t
aware that many OTC sunscreen 50 product be allowed to remain on the is less stressful than the sweat resistance
products with SPF values above 30 are market because it is needed for the test.
currently marketed and are increasingly “ultrasensitive patient” and for patients The agency does not find the data
used by consumers. Numerous with “dermatological problems.” The submitted in the studies sufficient to
comments from health professionals. agency has previously discussed the use support the comment’s contention. The
consumers. and industry provide actual of high SPF sunscreen drug products to studies each comprised distinct subject
use information in support of SPF protect consumers with photosensitivity populations and addressed a single
values above 30 for what may be a diseases (58 FR 28194 28225) and the variable, i.e., the effect of water
substantial number of sun-sensitive need to provide data for such uses (see exposure or induced sweating on a
people in this country. Further. as section ILF. commetit 28 of this product’s SPF. Therefore. a cornparis&
numerous comments noted: (1) There is document) Bs the absorption spectrum of mean SPF values across studies is not
a lack of data to correlate higher than of a specific product, not necessarily the the appropriate measure ofrelatlve
SPF 30 sunscreen products wlth SPF. may be the more clinically “stress~’ associated with these variables.
corresponding safety problems, and (2) significant factor for such people. The’agency believes that a randomized.
modern formulatlon techniques have As discussed previqusly in this two-period crossover study design in a
resulted in higher SPF values using comment 29 of section 1I.G of this single patient population.would better
lower active ingredient concentrations. document, the agency has concluded. have addressed the comment’s
Because of the numerousctsnr%-tt --: _ that the use of SPE label values above
from health professionals, new data,to contentbn; Further. the Pane& sweat
30 in OTC drug products is not and water resistance pmtocols provide
supporrthe need for SFF values above supported at this time. The agency,
30. and the lack of data concerning qualitative information and +ere not ___.
however. invites interested persons to
safety problems with such SPF values, designed to,provide comparatlve~
continue developing the test methods assertions requiring valid statlstical
the agency concludes that OTC needed to measure high SPF values, and
‘sunscreen drug products tiith SPF . inferences. Thus, the agency is allowing
to submit the data in support of such water and sweat resistant claims based.
values above 30 should be available for methods to FDA. If test methods are
those sun-sensitlve consumers who developed, the agency also invites upon the water resistance test
require such products b&d upon .. pmceduresln 5 352;76 of this
interested persons to consider proposed document. 1
personal knowledge of .theiiskln’s methods for communicating In labeling
susceptibility to sunbdm. experience the level of protection associated with 3 1. One comment c&tended that the
with specific products, planned sun high SPF values (given the nonlinear “water resistant” labeling pmposed in
exposure, or the recommendation. of a nature of the SPF rating system). These §352.5O(b)(l) and (c)(l) should not be
health professional. The agency agrees and other well-supported improvements required for products labeled or
with the comments that higher SPF 1 to the methodology for accurately and purchased for uses other ,than .
values generally can provide for greater reproducibly measuring SPF values will swimming or bathing.
relative exposure times and decreased be addressed. as appropriate. in future The agency notes that the water
UV mdlatlon transmission. However.. issues of the Federal Register; Until resistance statements referenced by the
the agency continues ta believe that the then. OTC sunscreen drug products are comment were not requited unless the
additional sunburn protection provided permitted to be labeled with SPF values manufacturer wished to make water
by an SPF 30 sunscreen and, e.g;. an no higher than “30+” or “30 piti.” resistant claims in the labeling of its
SPF 50 sunscreen (i.e.. about’s 1.3 - ‘Pinally. the agency does not agree sunscreen products. This final rule,also :
percent increase in absorption of with the argument that llmitlng SPF will not require a manufacturer to make
. e,rythemal UV radiation) is extremely values wouId stifle sunscreen product a water resistance claim for its
small’ for most people. The agency is development and prevent$lve health sunscreen product. even if the product
also concerned about the ability of beheflts. Undue emphasis for sunburn is determinedto be water resistant
current testing methods to accurately. protection should not be placed upon However, a manufacturer wishing to
and reproducibly determine SPF values SPF value alone (i.e.. “single focus make water resistance claims must
for high SPF products. (see section KM. products”). As noted by another comply with S§ 352.50(b) or (c)‘and
comment 53 of this document). In comment. consumer benefit ls achieved- 352.52(b)(l)(ii) or(b)(l)(iii) of this
addition, nonlinearity of the SPF rating through appropriate balance of several document. as applicable .for “water
system is a concept difficult to explain factors. including substantivity. UVA resistant” or “very water resistant”
in the limited space on a product label. radiation protection. and irritation products.
Therefore, the agency con&d& that the potential. .’ 32. Several comments urged the
label SPF declaration for sunscreens agency to return to the “waterproof’
with SPFvalues above 30 should be H. Comments on Water Resistant and “water resistant” label claims
limited to one collective term, which Labeling and Testing-for Sunscreen proposed .by the Panel and to limit the
appears in § 352.50(a) of this document Drug Products labeled SPF value to only the SPF after
as fo!lows:’ ‘*For products with SPF . 30. One comment agreed and several water resTstance testing. Another
values over 30. “SPF 30” (select one of disagreed with proposed i comment requested only general .
the following: “plus” or “+“I. Any § 35252(e)(2)(iii) and (e)(3)(&) . guidelines for claims such as “water
statement accompanying the marketed concerning sweat reslstant claims based resistant” or “sweat resistant” on the
product that states a specific SPF value upon water resistance testing instead of basis thatsuch cl&ns reflect the
above 30 or similar language indicating a specific sweat resistance test. One inherent characteristics of specific
a person can stay in the sun more than comment submitted data from two formulations and not sunscreen
30 times longer than without sunscreen sweat resistance studies and two water ingredients.
27676 ’ Federal Register/ Vol. 64, No. 98 /Friday, May 21. 1999/Rules and Regulations

The agency thoroughly discussed use In addition, the agency believes that for The agency agrees that solar keratoses
of the terms “waterproof” and “water consumers to compare products with are a clinical sign of skin damage.
resistant” in the tentative final multiple performance characteristics. a However, although sunscreens are
monograph (58 FR 28 194 at 28228). The labeling claim of “very water resistant” associated with a statistically significant
comments did not present any is best supported by a uniform testing decrease in solar keratoses after 1 or 2
arguments or data that the agency did standard. Shotild the agency receive years. the solar keratoses reduction in
not previously consider. In addition, the data in the future indicating customary this study was small and neither the
agency points out that performance usage patterns in excess of 80 minutes clinical nor biological significance of
claims such as these for OTC sunscreen of water exposure, it will reconsider this this reduction has been established.
drug products are based on final limit. Most solar keratoses never become skin
product formulation. 35. One comment disagreed with the cancers and typically resolve
The agency agrees with the comments agency’s proposal in the tentative final spontaneously (Refs. 27 and 28).
that the more relevant SPF value for monograph (58 FR 28 194 at 28278) that Because of the wide variability
products labeled.“water resistant” or manufacturers determine the waiting possible in the formulation of sunscreen
“very water resistant” is the SPF value periods for the most effective use of products. not all sunscreen products are
of the final, product formulation their sunscreen products (i.e.. the time identical in their W radiation .
following water resistance testing. between application and exposure to the absorptioncbaracteri&s. Sunscre& . .
Therefore. in this document the agency sun or water, if applicable). This .products may contain active ingredients :
is limiting the SPF label declaration to information would then be included in that absorb in different regions of the
the SPF after water resistance testing the directions for the product. The’ WB radiation spectrum (the primary
and is modifying the testing procedures’ comment asserted there is no reason to ,cause of sunburn) or absorb ,&I both the
in § 352,.76 ‘to reflect deletion of the : require a “time versus efficatiy” study WB and different regions of r&e WA . .
‘proposed dual SFF.testing requirement for every sunscreen
. formula because md&@on spectrum. Therefore.~even.rhe ‘.
- for sunscreen products Miith water degree@pe of W radiation.prot+tion ... .
resistant claims. their kfficacy for up to 8 hours. reportedin one study using a Speci@c :. . . .
33, Two comments suggested that In the tentative final monographt the
“water resistant” labering be permitted sunscreen formulation may not be ;
agency did not propose a specific.” relevant to alJ possible suns@en
for drug productsretaining at least 80 method or testing procedure for the
percent of their SPF value after static products w?rin the sCope of this final. . ; 1,
determination of a proper waiting monograph. Furt&r, the agency does
testing in ~001s and that any product period because of the variation in
meetingthis criterion could also be suns&& product dosage forms and oat believe that it, is prudent to
labeled “sw&t proof.” The comments fomiulations. Instead, the agency extrapolate claims for skin cancer or
further suggested that the term “very .allow&i manufacturers to make this skin aging based upon a test designed to 1
water resistant” shoulli be permitted for deter&nation. However. the agency. did only measureerythema (i.e.;tbe SPF . .
products retainb-rg 90 to 98 percent of . propose in.§ 352.52(d) (2) that a waiting test).
their SPF aftertesting. period before sun or water exposure, if The agency l&s reviewedinform&iori .
The agency disagrees with the . applicable, be included in the labeling concerning the mechanisms of skin .
comments. Simple imme,mion provides of sunscreen pmducts for their most cancers and photoaging. UV radiation
neither an aqueous shear stress nor effective use. Iti this final rule:the appe& to have a dual role in the
thermal challenge, and thus is an agency has included the requirement for induction of skin cancet% as it can cause
inadequate-assessment of water a waiting period in the stmscmen several varieties of direct DNA damage
resistance. In addition. no justification product application statement in . (Refs. 23 and 29 through32) plus .’
’ was offered for the respective threshold proposed $352,52(d)(l) for.the reasons suppress the immuneresponse to . . I
values of 80 percent and 90 to 98’. . stated bi the tentative fi rG1 monograph developing skin cancers(Ref& 33
‘percem. (58 FR 28278). The agency continues to through 37). This immune suppression
34. Several commens contended that allow the manufacturer to determine may be a critical .variable as skin : .
the water resistance testing procedures both the necessity for this statement cancers, unlike other cancer types: .
b-r § 352.76 should be amended to allow ‘(b&ad on the product’s formulation and evoke a strong immune response
for continuation of the water’exposure dosage form) and how the waiting (especially by Langerhans cells and T-
regimen beyond the 80 minute total and period. if appRcabIe. is determined. lymphocytes) (Ref. 38). In photoaging. ”
suggested that the “very water resista& there are multiole sites in the skin that
claim be expanded beyond 80 minutes I. Comments on indications for can be damaged by W radiation (Ref.
for products meeting such testing Sunscreen Drug Pmducts 17). For example, recent studies support .
requirements. One comment provided 36. One comment urged the agency to the concept that specific UV radiation-
data (Ref. 24) to support extended water more strongly state the effectiveness of.. induced enzymes (i.e.. matrix
resistance claims. Another comment sunscreens (a specific claim was not metalloproteinases) c+h mediate
also proposed a testing protocol (Ref. suggested). The comment cited a connective tissue damage and result in
25) for an additional claim of . controlled study of a broad spectrum, the premature aging effects seen in skin
“rubproof * or “abrasion proof.” SPF’ 17 sunscreen on 431 Caucasian. exposed to W radiation (Refs. 19 and
The agency does not concur with an subjects over one suirrmer in Australia 20). These data also suggest that these. .
expansion of the “very water r&stant” (Ref. 26). The study showed that the mechanisms of carcinogenesis and
claim. Although data submitted by the group using the sunscreen had photoaging can occur from doses of UV.
comment (Ref. 24) show that under significantly fewer solar keratoses and radiation below that required to produce
testing conditions products may retain more remissions than the control group. sunburn (Le.. suberythemal doses).
their SPF values for up to.270 minutes Another comment expressed concern Thus. even if no sunburn has occurred .
of water exposure, no usage data were that use of the term “help prevent skln with the use of a sunscreen, the
presented to refute the Panel’s damage” may mislead consumers to .consumer cannot assume that sun-
determination of an 80 minute upper think that these products prevent skin induced skin damage that might
exposure limit (58 FR 28 194 at 28277). cancer and premature skin aging. contribute to the eventudl-development
Federal Register/ Vol. 64. No. 98/Friday, May 21. 1999 /Rules and Regulations 27677

of skin cancer or signs of photoaging has For the same reasons. the agency also 39. Several comments contended that
not occurred. considers extended wear claims he extensive labeling proposed in the
The agency agrees with the comment corrcerning a specific number of hours entative final monograph was
that terms such as “help prevent skin of “protection” (or similar terminology) :xcessive. For environmental concerns.
damage” may mislead consumers to or an absolute claim such as “all-day .he comments objected to the use of
think that .sunscreen use alone will protection” to be nonmonograph. extra packaging materials as a method of
prevent skin cancer and premature skin Instead. the agency is including an ncluding added Labeling. One comment
aging. However. the agency believes that accurate. simpler, and less confusing disagreed with the need for a specific
an appropriate statement can be used to indication statement in this final rule statement of product indications on
inform consumers that sunscreens may using two bulIeted statements under the individual units of non-beach products
reduce the risks OFskin aging. skin “Uses” heading, as follows: “[bullet] properly labeled with an SPF value. and
cancer, and other harmful effects from helps prevent sunburn” and “[bullet] cited limitations on labeling space. The
the sun when used in a reguiar program higher SPF gives more sunburn comment suggested that manufacturers
that includes limiting sun exposure and protection”.r be given the option to provide off-
wearing .protective clothing (see section 38. Several com.ments contended that package information at the point-of-sale
ILL. comment 5 1 of this document). terms such as.‘skin aging.” rather than be required to place-the
37:Several comments expressed “wrinkling.” ” premature skin aging,‘! or statement(s) on each individual. unit of
concern that the statements “Allows “photoaging” should be permitted as the product.
you to stay in the sun up to (insert SPF indications for sunscreens, especially if To balance the environmental and
of product up to 30) times longer than protection is provided in the WA II regulatory concerns. the, agency has
without sunscreen protection” and (320 to 340 nm) radiation region. One, streamlined labeling in this final
“Provides up to (insert SPF of product c.omment suggested that a label claim. monograph by significantly reducing the
up to 30) times your natural protection * such as “Helps reduce the chance of amount of required labeling and making
from sunburn” in proposed * skin aging caused by incidental (or optional other labeliig thatwas
§ 35252(b)(l)(iii) and (b)(l)@) may casual) exposure to the sun” may help proposed as-required in the tentative
..mislead consumers as to the amount to further position the product asa final monograph. The agency is also _ .
and degree of protection sunscreen cosmetic for consumers. The comment including § 352.52(f) in this fina!
. products provide. The comments were also suggested an indication statement: monograph to provide for additional ‘. ._
concerned that this message will convey “Excessive. chronic sun exposure can labeling accommodations for sunscreen
a more expansive meaning than lead to premature photoaging of the products that meet the small package
intended and that consumers might be skin, characterized by drying, wrinkling specifications in S ZO,l.66(d)(lO) and are
. misled about how long they can stay in and thinning of the, skin. Regular use of labeled .for use on specific small’ areas T
*he sun without riskingany sun- a sunscreen can help protect against this of the face (e.g.. lips~nose. ear%.and/or
induced skin injury. One comment condition.” around eyes) (see section IV. comment
expressed additional’concem because. The agency d&z&sed theuse of terms 6ofthisdocument). - .
the SPF value is only a laboratory test such as ‘%cin aging;” “wrinkling.”
of a few minutes.duration. * “premature skin aging.” or J. $hnments on Wamil?gs~r Sunscreen-
One comment also. objected to the “photoaging” on sunscreen’products in Drug Products
unqualified use of terms such as . ’ the tentative finaLmonograph (58 FR .4O:‘One comment asked the agency to .
“shields from.” “protects from.” 28194 at.28236 and 26287):As’. permit reducedwarning statements for
“filters” or “screens out” the ‘sun’s discussed in the response to comments lip balm products containing sunsa~&
” “sun’s harsh rays.” or “sun’s 36 and.37, the agency has determined based on their safe market history. The
k%fuL rays” to *‘help prevent skin that the labeling should describe the comment argued that lip balms are not
damage” proposed Ln § 352.52(b) (l)(v) product’s use in preventing sunburn. A applied to the eye area, and thus
and (b) (1) (vi). The comment expressed more expansive set of itldications is extensive eye warnings arenot required-
concern that these unqualified terms currently unsupported. The agency Two comments cited the long history of -
could,imply complete protection from notes, however, that the RnaI “Sun safe use of lipstick products containing
the sun’s harmful rays and may mislead ‘alert” statement (discussed In section suns~ and suggested the reduced
i consumers by inducing a false sense of 1l.L. comment S1 of this document) does warning. “Discontinue use if signs of
’ sec.urity when using sunscreen provide the consumer with information irritation appear.”
products. about the role of sunscreens in reducing The agency discussed its rationale for ”
As discussed !n section &I. comment skin aging. in a context that ensures that proposing an eye warning for sunscnzn-
-36 of this document, the agency.believes the information will not be misleading. containing lip balms in comment 52 of
that sunscreen use alone will not The agency, however. is continuing to the tentative final monograph (58 FR
prevent all of the possible harmful consider whether certain sunscreens 28194 at 28229 to 28232).noting that
effects due to the sun. Variation may provide protection against . some lip balms could be used on other
between individuals. UV radiation photoaging (58 FR at 28267) and has areas of the face. Hovriever. the agency
absorption and substantivity of discussed this in tentative final has received neither data concerning
sunscreen products. exposure monograph amendments for certain adverse reactions due to the use of
conditions, and conditions of use sunscreens containing avobenzone’or sunscreen-containing lip balms near the
cannot promise a precise result for each zinc oxide based upon specific data eyes, nor information that such produe
Individual. Thus. the agency agrees that submitted to the agency (see.section 1l.E. are normally used in the eye area. These
these statements could provide the comment 22 of this document). The products also are consistent with the
wrong message and a false sense of agency will evaluate this issue further .factors described in the final OTC
’ security to some consumers. The agency .when it completes the UVA portion of standardized content and format
therefore is not including proposed the sunscreen monograph. in a future labeling rule (64 FR 13254 at 13270) for
§352.52(b)(1)(iil) through (b)(l)(vi) In issue of the Federal Register. considering additional labeling
this final rule and considers these and modifications. Accordingly. this final
similar statements to be nonmonograph. ‘See §201.66(b)(4) monograph allows sunscreen-containing
27678% Federal Register/Vol. 64. No. 98/Friday. May 21. 1999/Rules and
., Regulations
lipsticks to omit the eye warning in more concisely. as follows: “For products is unlikely to have serious
proposed §352.52(c)(l)(i). As discussed external use only. Keep out of eyes. If consequences.
in Section 1I.J. commeni 42 of this contact occurs, rinse thoroughly with The agency has determined that
document. the wording of this warning water. If irritation or rash occurs. directions for use in the labeling of
is modified in this final monograph. For discontinue use. Consult a doctor if lipstick products containing sunscreens
lip balms. the agency expects to adopt problem persists.” would provide minimal benefit to
the same modification when it issues Since the tentative final monograph . consumers and the omission of a
the final monograph on OTC skin was published. the agency has directions statement is not likely to have
protectant drug products. published a final ruie revising the ..I serious consequences (see section 11-J.
The proposed warning in format and content requirements for comment 40 of this document).
§ 352.52(c) (I) (iii) is now stated as a OTC drug product labeling (64 FR However. the agency believes that
bullet under the “Stop use and ask a 13254). Section 201.66(c)@)(i) requires directions would be useful for make-up
doctor if’ subheading as follows: the warning “For external use only” for products containing sunscreens because
“[bullet] rash or irritation develops and all topical drug products not intended of the wide variiq of make-up products
lasts.” This warning appears in for. ingestion. Therefore. it is not that are available. Therefore. the. agency
5 352.52(c)(I)(ii) in this document. 9ecessary to state that warning in this: is revising proposed § 352.52(d)(4) t0
Finally, lipsticks (and lip balms. which document and the warning in proposed read: “For products formulated as i
will be addressed in the final 5 352.52(c) (1)0) is not included in this lipstick. The directions in paragraphs
monograph on OTC skin prottictant drug final monograph. The agency is (d)(I) and (a) (2) of this section are not
products) will not &. required to bear shortening the pmposed waming in required.*’ The agency expects to
the “For external use only’ warning. § 352.52(c) (1)(ii). This warning appears finalize the same modifications for’ lip
Accordingly, in this final monograph, in §352,52(c)(l)(i) iii this document as balm products .tihen it final&s the .
§ 352.52(c)(2) allo& lipsticks to omit. a bullet under the “‘Wheti iising this monograph for OTC skin pmfectant.
the warning in S 20 1.66(c) (5) (i) . product*’ subheading as follows: drug products. . _’
4 1. One comment requested that an “[bullet] keep out of eyes. Rinse.with
&ye ikitancy warning.need.not be. . . 45. Sev+-al comments contended that
.-water to remove.” The agency is stating the proposed. dinzction. “Chtid&n under
required for-products that contain thepmposedwamingin -
titariitim dioxide as the sole active 2 years of &ge should use sunscreen
8 352,52(c)(l)(iii) as a bGllet under the products with a minimum SPF of 4,” is
ingredient. The comment stated that “Stop us& and ask a.doctor if’
titanium dioxide is.an inert inorganic misleading and has no s&ntific basis.
subheading as follows: “[bullet] rash or Z&me commenti stam that ti,e
oxide (and thus is chemically distinct irritation develops and lasts.‘:This
from all other Category I sunscreen” direction implies that &-I SPF 4 may be .
warning appears in §352.52(c)(l)$i) in adequate for &Wren z&d noted that the
aciive ingredients, which are organic’ this document. Section 201.66(&)(5)(x)
zompounds) and is an FDA approved Skin Can&r Foundatio% advi& we of
requires the “Keep out of reach of SPF $ or higher for both childreh an@
color additive.for the eye area in both children” and qcidental ingestfori
drugs and cosmetics. The cornme+ warning set’ forth in 2 1 CFR 330-l@ for advlts. The American Acadtiy of _
argued that determination of eye these products. Dermatology questioned why children .
wtancy should be Used on total 43.One.comment contended that’the should not .have the benefit of a more
product formulation. A second proposed warning about swallowing.in highly protective sunscree cl. other
comment cdncurred $at the ,&be&g foi § 352.52(6)(l)(i) would not be needed for comments suggested&at this dir&tion.
inorganic sunscr(?ens. which are not eye so-call& secondary sunscreen products should only be required for products
irritants. should be diiferentikted from betie adults using these products with‘an-SPF lower t&n 4 because it
organic stinscreens, which may be (which. accoiding to the comment, have. wouldbe nonsensical and a waste of
irritants in the eye. traditionally been marketed as label space on pm+zts with higher SPF
values. ..
The agency agrees tha; the eye cosmetics) would knoti not to ingest
warning (proposed in S 352.52(c)(I)(i$) them. The agency ag&es with the commLnti
is basfd on total formulation, not simply As discussed in section II j. comment that thti direction Could ml&ad parents
presence of an ingredient. The agency’s, ‘42 of this document, the wamirig into belieWig SPF 4 is adequate for.
rationale was discussed in comments 52 proposed in § 352.52(~)(1)(4 hss been children under 2 years, of age. Therefore.
and 62 of the tentative final’monograph. sup&seded by the warning reqdired by the agency concludes it is not
(58 FR 28194 at 28229 to 28232 and S 201.66(c)(5)(1). The new required appropriate and Ls.not including,it in
2824 I). Accordingly. this final warning no longer contains the. 4352.52(d) in this document.
monograph requires all sunscreen- statement about not swallowing the 46. One comment stated that the
containing drug products to, bear the eye product. words, “adults and children 6 tionths of
warning in 5352.52(c)(l)(i). Only age and over’: in prop&d 5 352.52(d) (1)
products formulated as a lipstick (and K. Comments on Directions for are unnecessary becam there .is a
Lip balms, which will be addressed in Sunscrew Drug Pro&cts separate statement, “Children under 6
the final monograph on OTC skin 44. Two comments stated that’ the months of age: consiilt a doctor.”
pmtectant drug products) m&y omit this proposed directions in 8 352,53(d)(4) fqr Another comment suggested that
warning (see S 352.52(c)(3) of this lipsticks and make-up preparations are lengthy directions for use by ohildren 6
document). The agency will consider unnecessary because these products are months to 2 years of age are not
omitting the eye warning requirement marketed primarily for their,cosmetic appropriate for many product types
for a particular formulation if data uses, which are self-evident. One (e.g.. a daily facial mtiisturizer with a
submitted in an NDA deviation comment contended that it is urilikely- _ sunscreen) and shoy!d _ _be revised
- to
(§ 330.11 (2 1 CFR 33O:i 1)) from the that consumers will modify their habits “For adult use only.-- Another comment.
sunscreen monograph demonstrate it is of lipstick application and usage simply added that when “For adult use only”
not an eye irritant. because the product contaiw a is used. then warning and cautionary
42. One comment suggested restating sunscreen. The other comment argued statements concerning use by children
the proposed warnings in § 352.52(c)(1). that failure to follow directions for these would not be needed.
Federal Register/ Vol. 64. No. 98 /Friday, May 21. 1999 /Rules and Regulations 27679

The agency agrees with the comment submit that information for approval via the agency is not including the
that the statement. “Children under 6 an NDA deviation as provided in recommended sunscreen product guide
months of age: consult a doctor.” g330.11. in this document.
provides sufficient information 5 I. Many comments requested that
regarding the age limit for use and is L. Comments on Product Performance the “Sun alert” in proposed
retaining it under 5 352.52(d) as a bullet Statements for Sunscreen Drtig Products § 352.52(e)(6) be voluntary instead of
with a small modification as follows: 49. Several comments recommended required labeling and suggested this
“[bullet1 children under 6 months of revisions to proposed §352.52(e). the information could better be
age: ask a doctor”. Therefore, the agency statement on product performance. For disseminated at the point of purchase or
is removing the phrase, “Adults and example, some comments suggested that through consumer education programs.
children 6 months of age and over.” The multiple superlative category Some comments stated that the “Sun
proposed directions for children 6 designations (e.g., “high.” “very high.” alert” is too weak and suggested
months to 2 years of age referred to by and “ultra high”) may foster consumer alternate language. One comment
the comments in-§ 35252(d)(l). (d)(2). confusion about the level of protection observed that the “Sun alert” fails to
(d) (3). and (d) (5) stated: “Children each SPF provides. Other comments warn consumers that UV radiation may
under.2 years of age should use stated that the current SPF scale does. harm the immune system..impairing the
sunscreen products with a minimum not encourage consumers to use higher body’s ability to fight Infectious dPease.
SPF of 4.” As discussed in section ILK, SPF products. Other comments The comment did not provide data to
comment 45 of this document, the disagreed with the indication “permits support this claim.
agency concluded that this direction no tanning.” The agency agrees that the “Sun alert”
was misleading and did not include it The agency has revised proposed should be.optional on product labeling.
in-§ 352.52(d) in this document. The § 352.52(e) in this document by Further. the agency has .reevaltited the
agency finds it unnecessary to- include condensing the five proposed product “Sun alert” and concludes that its
the direction “For aduit use only” in categories to three broader ones, and has purpose should be to describe the role I
this document because there are only generalized the category designations, of sunscreens in a total~prograni to
two age groups in the directions: The new categories are: minimal reduce harmful yeffectsfrom the sun.
Children under 6 ‘months of age and all . sunburn Protection for Products with- Marks (Ref. 39) hasnote@that.
other users of the product. - SPF 2 to under 12; Moderate sunburn sunscreens “are normally recommended *
47. One comment argued that the ’ . protection for products’withSPFi2 to for use as’an adjunct to other . *
direction “apply generously” may be under.30: high sunburn.pmtection for pmtection.” such as clothing. hats. and
responsible for some skin irritation products with SPF 30 or above. These avoidance of the sun near midday. The
complaints from consumers. However, product category designations (PCD) agency agrees with this concept. as do
the comment did not provide data to should appear under the “Other many researchers (Ref. 40). the
support its position. The’comment information” heading and may also American Academy of Dem~tology
contended that application of small& appear on’the PDP. Further, products (Ref. 41). Centers for Disease Control .’
amounts of sunscreen may.ptovide are.now described as prdviding (Ref. 4 1). and the Covemm&nts of
adequate coverage, but that in the case minimal, moderate. or high protection Australia and New Zealand (Ref. 42).
of sun protection, it may be best to err against tanning, thus deleting the For this reason, the agency has revised.
on the generous side. Another comment reference to tannine oreventlon that was the “Sun alert” to include other
maintained that applying too little proposed in §352.52’cb)(2)(v).(B), ~. protective actions consumers can take,
sunscreen may significantly lower 50. Many comments o~msed the and has clarified possible results. The
protection in a’geometrlcrather than a “recomme;lde‘h su tlscre&prcduct agency is including skin cancer in the .
Itnear fashion, e.g.; an SPF 25sunscreen g&de” in pmposed’§352.52(e)(4). Some “Sun alert” instead of the body’s abllity ,.
applied half as thick as the amount comments noted that the guide is tb fight infectious disease because, to
applied for the SPF test may only have incomplete because it only considers date, skin cancer ls the best dooumentecl
the effect of SPF 8. skin type and not dumtion.of exposure, adverse effect of UV radiation on&e
The agency agrees with the comments ,seasorx,geographic location, and other immune. system (Ref. 43). Accordingly: -
that &iequate sunscreen should be factors that influence choice of product. S 352.52(e)(2) in this qocument provides
applied to achieve full labeled SPF Other comments stated that the guide is the following optional “Sun +rt,*’
protection. Therefore, the agency deceptive and may encourage which should appear under the “Other
concludes that the dli-ections in inappropriate use of lower SPFs for information” heading and may also
S 352.52(d)(l) of this final monograph to protection. Several commentsstated. appear on the PDP: “Limiting sun
apply “liberally” or “generously” that labeling for many Products is too exposure, wearing protective clothing.
convey the appropriate message to small to accommodate the guide. Other and using sunscreens may reduce the
ensure that.consumers adequately apply comments suggested that information in risks of skin aging, skin cancer, and
the sunscreen. the guide should be disseminated to other harmful effects .of the sun.” The
48. One comment stated that the consumers through Point of sale, agency encourages sunscreen
agency should permit firms to provide television, and weather programs, rather manufacturers to voluntarily include
reapplication instructions based on than being required in product labeling. this “Sun alert” in the labeling and to
substantiation information the firm The agency recognizes that various otherwise make it available at point of
possesses, The comment noted that factors influence the purchase of a purchase and through consumer
some products may not need to be sunscreen product, including skin type. education program;
applied as frequently as some select geographic location. hours exposed to 52. Several comments sueeested that .
time period. the sun. and sun-reflections. While the the term “sunblock.” pmpozd in the
The agency is including a general pmcluct guide was intended as a general definition in § 352.3(d) and as a labeling
reapplication direction in § 352.52(d)(2), guidance for using these products. the statement for products containing
Manufacturers who have data to support agency acknowledges that the guide ls titanium dioxide that provide an SPF of
reapplication instructions based on incomplete and could be confusing and 12 to-30 in §352.52(e)Q. not be
specific substantiation information may misleading to consumers. Accordingly, included in the ftnal monograph. Some
27680 Federal Register/Vol. 64. No. 98/Friday, May 21. 1999/R&s and Regulations

comments argued that- the term is tvf. Comments on Testing Procedures for equation. Another comment stated that
unclear and may mislead and confuse Sunscreen Drug Products the definition of E is incorrect because
consumers into thinking that the 53. Several comments questioned the it is defined as “dose” (Joules/square
product blocks all of the sun, when in ability of current testing methods to meter (ml)) on the left side of the
fact it does not. One comment stated accurately and reproducibly determine equation E = X V; (71)* 1 (A). whereas the
that no product available totally blocks SPF values for high SPF products. Some right side of the equation is in terms of
sun damage. Numerous other comments comments contended that the spectra of irradiance (Watts/m2). The comment
contended that the term “sunblock” also stated that the unit of time
currently used solar simulators
should be applied to all sunscreen (especially around 290 nm and above exposure [seconds) is missing on the
ingredients that provide an SPF of 12 or right side of the equation.
350 nm) could cause overestimation of The agency acknowledges that this
higher, as such products block at least SPF for high SPF sunscreens and
90 percent of the sun’s UV rays. One of calculation is not technically necessary
recommended use of a specifications if the solar simulator emission spectrum
the comments submltted a study (Ref. table that provided percent of erythemal
44) to shpw that micronized titanium does not change between exposures to
contribution by wavelerigth regions. protected and unprotected skin. The
dioxide absorbs short wavelength UV Other comments submitted data in
radiation and reflects and scatters long same result can then be obtained b
support of a.high-SPF sunscreen control measuri.ng the difference (i.e.. ratio J in
wavelengths, thereby functioning following concerns expressed by the
similarly to. chemical UVEI radiation time required to produce erythema on
agency in the proposed rule (58 FR protected versus unprotected skin.
sunscreens. The commem dontended 28194 at 28253 and 28254) that data
that the method in which micronized However. the agency finds that the
were not sufficient to demonstrate that calculation of E provides valuable
tltan+m dioxide @erforr& as a the testing’methdds used,to evaluate
sunscreen active ingredient fiuther Jnfo*+n. and..% new to ._ _ -.- _ -, :.
sunscreen drug products with SPF .c@onsmte h.0.w..the.MED. was
justifies the use of the term “sunblock” values .up to 15 are equally applicable determined during
1for all suns&een prbdudts .with an SPF to evaluating sunscreen drug products ._ SPF
_ t&sting. The ’
agency a@+ wi? the cQn+ent
of 12 or higher. with SPF \ialues above lfi.Several- .. ..- . c&eining the missing variable of time . ..
The agentiy has decided not to comments submitted data and (in se&r&) in the calculation’ of E and.
include the term “sunblo& in the final information that questioned t&e ability a~~oidinglfr. has moQified the eqqtion
monograph and now considers this term of currerit testing methods to accur@ely in 5 352.73 of thii document to’read 9
nonmonograph. The agency’s intexition and rep+ducibIy determine SPF values follows: “ E = Z Vi (X) + I (L) * t+” .
. In the tentative final monograph was to for high SPF produc+ and requested
provide information tq consumers on significant changes to proposed subp,art III. Recent Develop&ents
the mewed of .product$erformance. not Q of S 352.X. Other commenti 1.nthe Federal.Regi&er of O&o@% 22.
to imply greater pmtection from.@ng a requeSted changes to the testing 1998. the agenq proposed to e&d the ..
product labeled as a “sunblock!’ The procedures proposed in subpart D of the tentative fmal monograph to include
agency Lsconcerned that the terin sunscreen monopph that.were ztic oxide as a single ingredient and in
“sunblock” on’the label of sunscreen unrelated to produ$s with high SPF combination with any proposed T
values. . Category I sunscreen active ingredient
drug products will be viewed + an
absolute term which may r&&ad or The agency believes that the test. except avobenzczne. Two commenti
confuse consumers into thinking that inethod proposed in the tentative final supported *e proposal. One comrilent ._
.the product blocks all light from the monograph (TFM). for measuring SPF . dieed with the agency’s exclusion df
sun. For example, consumers might val@s up to. 30. represents at this time avobenzone from combinations with
view an SPF 15 product labeled as ‘a a s@aightforward, well-understood, and zinc oxide. Two’of the comments urged
iunblock as superior to a product sound inethod for measiuing these . the agency to expeditiously review and
labeled as an SPF 30. broad spectrum :, tialues. The agency the&ore is . approve a citizen petition (Ref. 49 .to .
suns$reen. As nonmonograph labeling, finalizing the method proposed .in tlie recognize t$s combination.
PM. The 3get-q recognizes, however, The.agency has informed the
the .t~ “sunbIock” cannot appear that testing methods in this area are
anywhere in product labeling. petitioner that it is tinable to appro+e
evolving and that a number of the combination without appropriate I .
In addition, the proposed definitio’n .of comments raised useful ideas for UVA radiation effectiveness data to
‘*sunscreen opaque sunblock” in proposed improvements in the accuracy demonstrate the UVA radiation
§ 352.3(d) applied only to titanium and reproducibility of the agency’s pmtectidn potential of zinc oxide in
dioxide and is inconsistent with how methodology.. As discuss& in response combination with &obenzone (Ref. 4.$),
micronized titanium dioxide functions to comment 29 of section KG of this The qency will reconsider this
as an sunscreen active ingredient (Ref. doctiment. the agency is also inviting combination for monograph status upon
44). Further, it is the radiatiqn from the interested persons to continue working receipt of the appropri$te-da@.
UV portion (290 to 400 nm) of the sun’s on imprdving SPF Mting methods, ’ This final rule includes monograph
spectrum that reaches the earth’s surface toward the development of accurate ., conditions for zinc oxide as a suisireen
and may produce skin erythenia. methods for measuring high SPF values. active ingredient at concentrations up to
melanogenesis. and cancer. The agency In future issues of the Federal Register, 25 percent when used alone or in
believes that claims of protection if appropriate, the agency will consider combin%tion with any monograph
beyond 400 nm (i.e.. prottition from proposed improvements to .its testing sunscreen active ingredient except
visible and lnfra red light) are methodology. avobenzone.
nonmonograph and not within the 54,. One comment contended that the
scope of this document. Therefore. to calculation of erythema effective &/. Additional Changes
pmiride clear and cons&tent labeling. exposure (E) serves no practical purpose 1. The agency has deteimined that for
the agency is not including proposed in the calculation of SPF because the E an active4ngredient to be included in an
~~~~~~~) and 352.52(e)(5) in this constant is common to both the OTC drug final monograph it is
numerator and denominator of the . necessary to have publicly available
Federal Regisler/Vol. 64, No. 98 i Friday, May 21. 1999 /Rules and Regulations 27681

chemical information that can be used references to any other indication §35252(b)(l)(ii) and (b)(lJ(iii) in this
by at1 manufacturers to determine that except that pertaining to the prevention document.
the ingredient is appropriate for use in of sunburn (see section 11.1.comment 37 5. The agency has modified references
their products. Compendia1 monographs of this document). (2) adding (in to “tanning” and “prolongs exposure
include an ingredient’s official name, § 352.52(b)(2) of this final rule) guidance time” in proposed § 35252(b)(2) by
chemical formula. and analytical on SPF selection due to simplification combining the PCD claim in
chemical tests to confirm the quality of the PCD in proposed 5 352.52(e)(I) § 352.52(e)(l) of this document with
and purity of the ingredient. These and deletion of the Recommended either the phrase “protection against
monographs establish public standards Product Guide in proposed sunburn” or “protection against
for the strength. quality, purity, and § 35252(e)(4) (see section ILL. sunburn and tanning.” Based upon
packaging of ingredients and drug comments 49 and 50 of this document). current information, the agency believes
products available in the United States. and (3) deleting the quantitative claims that the terms proposed in the tentative
In the Federal Register of June 8, (i.e.. “up to (insert SPF of product up to final monograph could send the wrong
1994. FDA deleted digalloyl triobate. 3@)times”) and terms such as “screens.” message relative to the dangers of even
ethyl 4-[bis(hydroxypropyl)] “shields,” etc.. concerning sunburn suberythemal UV radiation exposure
aminobenzoate. glyceryl aminobeczoate. protection throughout proposed and give consumeis a false sense of
lawsone with dihydroxyacetone, and § 352.52(b) (seesection III. comment37 >ecurity concerning sun exposure and
red petrolatum from the tentative final of this document). sunscreen use. The agene has reduced
monograph due to the .lack of.interest in 3. The tentative final mdnograoh and simplified the other optional, .
establishing USP compendia1 allowed reduced labeling dir&i&s on additional indications $ proposed
monographs for these ing&iients. sunscreen products if form@ated as a S 352,52(b)(2)‘to reflect a modified,
Lawsone with dihyc+yacetone make-up preparation, lipstick. lip balm. siinpler. combined version of the PCD in
subsequently remained ,under agency or skin’ prepaWon and labled with 7 pmpos* S 352.52(e){ 1) (see section ILL.
considemtion due to .increased interest claims relating only to the prevention of comment-480f this docfiment) %t~ix;the
by manufacturers in establishing a “lip damage.” “freclding.” or “uneven “Recommended Product Guide” in
comp&ndial.monograph. Of the 18 - colbration.” Because there is no pmpo&d § 352.52(e) (4) (see section ILL.
remaining sunscreen active ingredients . convincing evidence that SPF testing comment 50 of’this document). Because
under consideration in the tentativk predicts protection fern anything but the agency has deleted reference to use
final monograph (58 FR 28194 at 28295, sunburn (seesection ILL comment 36 of of the term “Sunblock” in pmpo%ed
amended at 61 FR 48645 and 63 FR this document), !he agency is not section §352.52(e)Q (see section ILL.
56584). 16 (aminobenioic acid, including proposed S 352.52[b) (l)(v), comment 52 of thii d&ument) , it has
avobetizone; cirioxate. dioxybenzone, (b)(l)(vi). (d)(4). and’(d)@) in this deleted reference to, “Reflects the .
homosalate. menthyl anthyzmilate. $ocument. The agency will c&.sider burning rays of the sun” in .prdposed
octocrylene, ,octyl metfioxycinnamate.’ including such’ claims in the monograph § 352.52(b)(3) for the same reasons.
ociyl.salicylate. oxy.@enzone. padimate when specific supportive,data are .. 6, Sew@ comments requested
0. phenylbenzimidazole sulfdnic&d, provided or a.specific clinically reievant labeling exemptions or flexibility for
sulisbbenzone. titanium dioxide, final formulation test is developed. packages that are too small’ to
trolamine salicylate, and zinc oxide) 4. Numerous comments requested accommod& all requi+information.
currently hav.e compendia1 monographs. deletion of the dual SPF testing of water Some odmments specifically requested
Two (diethanolamine r&Mint produdts in proposed flexible labeling for products based
methoxycirinamat& and lawsone with § 352.50(b)(2) and (c) (2). The agency upon their intended use. such as :
dihydroxyacetonk) .do not have a current agrees with *e comments (see section lipsticks and li balms.
or proposed compendia1 monogra h. ji.H, comment 32 of this documeht) and As din the finai Nle
The ager?cy is including in S 35 B.I0 of has revised pmposed §S 852.50(b) (2) establishing $,tandardized formal and
this document the .le sunscreen active. and (c)(2) and 352.76 to’ require only the content requirements for the labeling of
ingredients that currently have a SPF value after water reSistant testing. OTC drug products (64 FR 13254 at
competidial monograph. The agency is Further, the agency has mo&fied~and 13267 to 13268 and 13289)..theagency
F@ng the appropriate paragraphs in inade optional the reapplication’ has established specifications for small
proposed 8 352.10 for the two active directions in proposed @352.52(d)(l) packages in § 201.66(d)(lO). The agency
ingredients without compendial and (d)(Z) (see section ILK. comment 48 also stated in the final labeling rule that
monographs in case a.monograph is of this document). These changes to it will consider additional approaches
developed for either ingredient. proposed 5 352.52(d) provide flexibility fdr accommodating certain small-
Dihydroxy&zetone has .&en proposed by allowing manufacturers to expand on package products in their respective ’
for a compendia1 mtinograph. butndne reapplication information necessary for OTC drug monograph proceedings.
has been proposed for lawsone. Because specific sunscreen formulations and by The aeencv tionsiders the reauir&i
these two active’ingredients areused in equalizing requirements between OTC &g IaGellng inf+nation’essentia
conjunction. lawsone must have a products with and without water for the safe and effegive use of these
compendia1 monograph in order for resistance claims and between products and important to consumers
lawsone with dihydroxyacetone to be sunscreen drug and drug-cosmetic for selection of an appropriate product.
included in the sunscreen final products. Thus. the water resistance Nevertheless, the agency agrees that
monograph. labeling in 5 352.52(b)(l)(ii) and excessive labeling requirements may
2. The agency has revised proposed (b) (l)(iil) of thii document should also discourage manufacturers from
S 352.52(b) in response to comments serve as a directive for reapplication of marketing certain products, such as
requesting reduction. streamlining, and the product. In summary. for products lipsticks or lip balms containing
flexibility of sunscreen labeling and tn .making water and/or sweat reststanbe sunscreens, which provide signtficant
accordance with new data reviewed by claims. the agency has modified and public health benefit.
the agency (see section I1.I of this combined water resistance,statements In this OTC drug rulemaking. the
document). The agency has revised formerly in proposed 5 352.52(e)(2). agency has included several
proposed S 352.52(b)( 1) by: (1) Deleting k)(3). (d)(l). and (d)(Z) into accommodations for products such as
27682 Federal Register/ Vol. 64. No. 981 Friday. May 2 1, 1999 I Rules and Regulations

lipsticks (and lip balms, w.hich will be §310,545(a)(29). or that is not in 13. PharmacoDeiaf Forum. United States
addressed in the final-monograph on conformance with the monograph (2 1 Pharmacopeial bnvention. Inc.. Rockvtlle.
OTC skin protectant drug products). CFR part 352). may be considered a new MD. 22(41:2635-2636. Julv throuqh August
taking into consideration the intended 1996.
drug within the meaning of section 14. Pharmacopeial Forum. United Stat=
uses of these products. the limited areas 201 (p) of the act arid misbranded under Pharmacopeial Convention. Inc.. Rockville.
to which these products are applied. section 502 of the act. Such a drug MD, 24(4):6547-6548. July through August
and the overall safety profile of these product cannot be marketed for OTC 1998.
products. and other factors described in sunscreen use unless it is the subject of IS. Comment No. COO406.Docket No.
the final OTC labeling rule (64 FR 13254 an approved application under section 78N-0038. Dockets Management Branch.
at 13270). The agency is including 505 of the act (2 1 USC. 355) and 21 16. Comment No. COO404.Docket No.
5 352.52(f) in this document to provide CFR part 3 14 of the regulations. An 78N-0038. Dockets ManagementBranch.
for. labeling modifications for sunscreen 17. K&man. L. H.. and A. M. Kligman.
appropriate citizen petition to amend “Ultraviolet Radiation-Induced Skin Aging.”
products that meet the small package the monograph may also be submitted in Sunscreens: Development, Evaluation. and
specifications in 5 20 1.66(d) (10) atid are in accord with 21 CFR 10.30 and Regulatory Aspects. Lowe. N. J.. N. A..
labeled for use on specific small areas §330.1O(a)(!2)(i). The agency will Shaath. and M. A. Pathak.eds.. Marcel
of the,face (e.g.. lips, nose, ears..and/or addreSs sunscreen act.&& ingredients . De&ker. Inc.. New York, pp. 117-137.1997.
around eyesf . that have.foreign marketing experience 18. Lavker. R. and K. Kaidbey. ‘The
7. The agency has revised S§ 700.35 and data at a future time.- Any OTC Spectral Dependence for WA-Induced
and 740.19 (21 CFR 700.35 and 740.19) sunscreen drug prodiict jnitially Cumulative Damage in Human Skin..“’ The
in response to comments requesting introducedor initially deliver& for Journal oEInvestIg&ve D~fmatology, 108il7-
clarification on whether certain 21. 1997.
introd+on into in&state commerce 19. Fisher. G. J. et al., “PathophysiologL of
products will be subject to regulation as after the effective date of the ftnal r&e
drugs (see section I1.B. comments 8 Premature,Skin Aging Induced by Ultravlole~
for’s 310.545(a)(29) or this document Light.” The New Engiand@urrlal of
through 11 of this document); Section that is tiot in Conipliance with the -Medicine. 337:1419-1428. 1997.
700.35 has been &vi&d to make cle& regulations is subject to regulatory 20. Lowe, N..J. et al., “Low Doses of &--- _- . . .I-
that, generally, products that make sun action. ReoetItive Ultraviolet A Induce Morphologic
protection claims; whether express or ChinEes & H&an Skin.” Joumai’oTthe
implied, are subject to regulation as VI. References Ame&an Acadeiny of Dennatolo@,
drugs. Only those products that contain The following references are 0~ 105:739-743: 1995.
. a sunscreen ingredihnt solely for a display in the Dockets Management 21. Comment No.COO28~. Docket No.
nontherapeutic. nonphysiologic use . Branch (address above) and may be seen 78N-0038. Dockets Management Bach.
(e.g., as a color additive; or to protect 22. CommentNo. COO365;DockTt No.
by interested persons between 9 a.m. 78N-0038. Dockets Management Bra&~
the color of the produc$‘such as in a nail and 4’p.m.,.Monday through Friday. 23. (hunem No. COO531. Docket No.
polish or hair coloring product) (see 5.8 1.CommentNo. CPL.DocketNo. 78N- 78N-0038. Dockets Managemtit Branch.
FR at 28205). and which include a ’ 0038. Dockets Manamment Branch. 24. Comment No. COO128.Docket No:
labeling statement tliaf accurat&ly 2. &nxnent No. C?Z, Docket NO. 78N- 78N-0038. Dockets Management &anch. ’
describes that use, may be marketed as 0038. Dockets Management Branch. 25. Gxnment No. SWIG. Docket No. 78N-
cosmetic products. Section 746.19.has 3. Comment No. CP3. Docket No. 78N- 0038. DocketsManagementBranch.
been revised to make clear that the term 0038. Dockets Manaeement Branch. 26. Thompson. SC.. J. D. Jolley,,and R.
4. comment No. &7. pocket No, 78N- Marks. “Reduction of Solar Keratoses by.
“suntanning preparations” does not 0038. Dockets h4gqement Bran&.
include products intended,to provide Regular sunscree n Use,” The NewEizgknd
5. Corn&e de Liaison des Assoclatlqns Journal 0fMeoYcfne. 329:X 147-l 151.1993.
sun protection or otherwise to affect the &ropeeries de L’IndwtrIe de Q Pa&me&e,
structure or any function of the bdy. des’produits CosmetIques et de Toilette 27. Marks. R et al.. “Spontaneous
.Remlssion of Solar Keratoses: The Case for .-
Suntanning preparations include gels, (COLIPA). SPFTest Meth~‘(Dca@. The
Recotiendatiom, tif the COLIPA Task F&ce ConsenmtiveManagement,” British Journal - .
creams. liquids. and ot+er topical of Dermatology, ! 15z649-654.1986.
products that are intended td provide “Sun Protection Measurement” December
1992 in Comment No. COO365.Docket No. 28. Marks. R. and G. Rennie. “Mal-ignant
cosmetic effects on the skin while 78N-0038. Dockets h4ana~ement Branch. Ttansforma~on of Solar Keratoses to .
tanning through exposure to W 6. Peak M. J.. and J.C. &n der Leun. squamous Cell CarclnO~” The LarXa?t
radiation (e.g.. moisturizing or “Boundary Be&en WA and UVB.” in 795-796.1988.
conditioning), or that are intended to F&Yes k Photobiology, edited by A. Shit&a 29. Komhauser, A., W. G. Warner, and L ,’
give the appearance of a.tan by et al., Excerpta Medlca. Amsterdam. pp. 425- Al Lambert, “Cellular and Molecuiar.Events
Imparting color through the-application 427.1993. Following Ultraviolet Irradiatitin of SW in
7. Comment No. LET 135. Docket 78N- Dermatototicology, F. N. Marzulli and HI.i.
of approved color additives (e.g., Maibach, eds.. Taylor & Francis. Washington
dihydroxyacetone) without the need for 0038.Dockets ManagementBranch.
8. Dunkel. V.C. et al., “Evaluation of the pp. 189-220.1996.
exposure to UV radiation (i.e., sunless Mtitagenlcky of an N-Nitroso Contamtnant of 30. Kraemer, K. H., “Sunlight and Skin
tanning products). the Sunscreen Padimate 0.” Environmental. Cancer: Another Link Re&!aled.” Proceeds af
if. Conclusion and Molecular Mutagen&s. 20:188-198. the National Academy of Sciences u. Z?.A.
1992. 94:l t-14. 1997. -
The agency is issuing a final 9. Comment No. CO0364. Docket No. 78N- 31. Hurks, H. M. H. et al.. “In Situ Action
monograph establishing condittons 0038. Dockets Management Branch. Spectra Suggest that DNA Damage Involved
under which OTC sunscreen drug 10. Comments No-CO0397 and SUP2 I, in Ultraviolc:‘Radiation-Induced
products are generally recognized as Docket No. 78N-0038. Dockets Management Imm&osuppression in Humans.”
safe and effective and not misbranded; Branch. Phqtochemistry and Photobiology. 66:76-8 1.
16 ingredients listed in 5 352. IO are I I. Fairhurst. D.. and M. Mitchnick. 1997.
“Particulate Sun Blocks: General Principl&.” 32. Bun-en. R. et al.. “Sunlight and
currently a monograph condition. Any In,Sunscreens: Development. Evaluation. and Carcinogenesls: Expresston of ~53 and
drug product labeled. represented, or Regulatory Aspecti, Marcel Dekker. Inc., New Pyrimldine Dlmers irrHuman Skin Following
promoted for use as an OTC sunscreen York. pp; 3 13352. 1997. UVA 1. WA I + II and SoIar Simulating
drug that contains any of the 12. Comment No. TR3. Docket No. 78N- Radiation.” International Journal of Cancer.
nonmonograph ingredients listed In 0038. Dockets Management Branch. 76:20 I-206. 1998.
Federal Registeer/Vol. 64. No. 98 /Friday, May 21. 1999/Rules and Regulations ‘ 27683
,.^ .’ .,
,T/. .,.,L_..
33. Hcrsey. P. et al.. “Analysis of the Effect Executive Order 12866 directs agencies cannot quantify the overall expected
of a Sunscreen Agent on the Suppression of to assess all costs and benefits of benefits. each provision of the rule will
Natural Killer Cell Activitv Induced in
Human Subjects by Radiakon from Solarium available regulatory alternatives and. support the ability of consumers to take
Lamps.” The Journal oflnvestigative when regulation is necessary. to select desired protective actions. Monograph
Dermatology. 88271-276. 1987. regulatory approaches that maximize ingredients have been proven safe and
34. Van Prague. M. C. G. et al., “Effect of net benefits (including potential effective assuring the quality of
Topical Sunscreens on the UV-Radiation- economic. environmental, public health sunscreen products. This benefits
Induced Suppression of the Alioactivating and safety. and other advantages; consumers because it ensures that the
Capacity in Human Skin In Vivo.” The distributive impacts: and equity). The product will provide ingredients that
Journal of Investigative Dermatology, 97:629- agency believes that this final rule is safely protect against sunburn. The new
633, 1991. consistent with the principles identified product labeling will better inform
35. Miyagi. T.. A. M. Bhutto, and S. in Executive Order 12866. OMB has
Not-&a. “The Effects of Sunscreens on UVB consumers about the sunburn protectloon
Erythema and Langerhans Cell Depression.” determined that the final rule is a provided by the products: and if
The Journal of Investigative Dermatology. significant regulatory action as defined manufacturers choose to include the
21:645-8~ 1, 1994. by the Executive Order and so ls subject optional “Sun alert” labeling statement,
36. Seite. S. et al.. “Effects of Repeated to review. Under the Regulatory the product labeling canreference that
Suber@emal Doses of UVA in Human Flexibility Act, if a rule has a slgnlflcant the use of sunscmens may reduce the
Sk~a,” Euqean~Jourtial of Dermatology. economic impact on a substantlal risk of skin aging, skln cancer. and other
7:204-209. 1997. number of small entities, an agency harmful effects of the sun. These
37. Lavker. R. M. et al., ‘Cumulative must analyze regulatory options that
Effects from Repeated Exposures to labeling requirements. ln conjunction
Suberythemal Doses of UVB and WA in
would minimize any sign&ant impact with the format requirements of the
Human Skin.” kumal of the American of the rule on small entitles. Title II of OTC uniform labeling rule (64 FR
Academy o~D&natology, 3253k2.1995. the Unfunded Mandates Reform Act 13254) .will provide clearer and more
38. Baadsgaard, 0.. “In Vivo Ultraviolet requires that agencies prepare awrltten concise information that wiii benefit
Irradiation of Human Sl& Results in assessment of antlclpated costs and consumers in at least fo.ur ways: (1) -.
Profound Perturbation of the Immune benefits before proposing any rule that They will increase‘understatiding
System.” .4r&ves of&rmato1o~, 127:99- may result in an expend&tire in.any I regarding the selection of sunstieen
109. 1991. year by State. local. and t&al drug products. (2) they will make
39. Marks. R.. “Reduction of Actinic governments, in the aggregate. or by the product comparison easier, (3) they will
Keratoses by Sunscreens,” in Sunscreens: private sector. of $100 miIIlon (adjusted enhance the abilitjr to make informed
Development. Evaluation. and Reguktov
Aspects. Lowe. N.J. N. A. Shaath, and M. annually for lnflatlon) (2 USC. 1532). decisions regarding product pu+ases
A. Path& eds., Marcel Dekker, Inc.. New Because the rule may have a and proper use. and (4) they will make
York. pp. 189-198. 1997./‘ significant economic impact on a it easier :o distinguish between
40. Dial. W. F.. “Mouse Study Creates . substantial number of small entitles. sunscreen drug products that contain
Coontraversy Over the .Uso of Sunscmens.” this section of the preamble constitutes sunscreens and suntannlng.products -.
Cosmetic Dermatology, 7~47-48. I994. the agency’s Final Regulatory Flexibility tlpt do not. Finally. the new
4 1. Goldsmith. L.. et al., “Pmceedlngs From Analysis. Because the ruIe does not
the National Conference to Develop a .. requirements for product testing will
impose any mandates on State, local, or assure the accuracy of the SPF value on
National Skin Cancer Agenda.” Journal of tlze tribal governments; or the private sector, the product label. By improving the
American Academy of Derfnamlogy, 34:822-
23.1996. that @ll result in an expenditure in any accuracy of-these ratings. this
42. Standards Australia&andards New 1 year of $100 million or more. FDA is requirement will provide further
Zealand. “Sunscreen Products--Evaluation not.requlred, to perform a cost-benefit assurance that consumers receive
and Classifitition.” ASfNZS 8604.1993. analysis according to the Unfunded adequate sunburn protection
43. Be&art, S. and R D. Gransteln, “W- Mandates Reform Act. f .
Induced Cutaneous Photobiology,” critical An analysis of the costs and benefits The rule wlllrequi~all ’ f
Reviews in Biocht@s&y and Mole&r of this. regulation. conducted under manufacturers and distributors (or their _
Blofogy 31:381-404. 1995. Executive Order 1229 1, was discussed agents) to relabel their OTCsunscreen
44:Sayre. R. et al.. “Physical S’unscmms.‘* in the tentative final monograph for drug products to comply with the .
Jourrial of the Socfety of Cosmetic Chemists. OTC sunscreen drug products (58 FR monograph language. The labeling of
. 41:103-109.1990, certain suntanning products that do not
45. Comment No. CP8. Docket No. 78N-. 28 194 at 28294). The agency received
~-
0038. Dockets M&-iagenientBranch. only one response to the specific request. contain sunscreens will need to include
46. Comment No. LETl66.Docket No. for data and comment on the economic the new required wamlngstatement. In
78N-0038. Dockets Management Branch. impact of this rulemaklng. This some cases, the labeling of cosmetics
47. Food and Drug Administration, comment discussed the costs that would containing sunscreens for
“Supplement to the Economic Impact result from proposed changes ln nontherapeutic. nonphysiologic uses
Analysis of the Sunscreen Drug Products for sunscreen product labellng and testing, (e.g., to protect hair from sun damage)
Over-the-Counter Human Use; Final methods. The agency’s review’of this will need to describe ‘the cosmetic role
Monograph.” in OTC Vol. 06FR. Docket No. of th,e sunscreen ingredient(s). The SPF
78N-0038. Dockets Management Branch. comment ls included as follows.
of some OTC sunscreen drug products
48. Eastern ResearchGroup, Inc., “Over- A. Background may need to be retested using the
the-Counter Drug Reformulation Changes,” in
OTC Vol. 06FR. Docket No. 78N-0038. The purpose of this document is to method described in the final
Dockets Management Branch. establish conditions under which OTC monograph. In addition. only products
sunscreen drug products are generally containing the active ingredients
VII. Analysis of Impacts recognized as safe. effective. and not included in this final rule will be
FDA has examined the impacts of this misbranded. The document sets specific generally recognized as safe. effective,
final rule under Executive Order 12866. reauirements for aonrooriate and not misbranded. Of the I8 active _
the Regulatory Flexlbillty Act (5 USC. monograph ingred&s~ labeling format ingredients under consideration in the
.60 l-6 12), and the Unfunded Mandates and content. and SPF value and water proposed rule. 16 currently have the
Reform.Act (2 U.S.C. 1501 erseq.). resistant testing. Although the agency required USP/N.F. compendia1
27684 Federal Register/ Vol. 64. No. 98 /Friday, May 2 1. 1999 /Rules and Regulations

monographs. The USP has not received already accounted for in the agency’s the agency assumes that half would &
applications for the remaining two analysis of its OTC drug product redesigned every 3 years and half every
ingredients. If either of these active labeling rule. That is. the agency’s 6 years. &cause the required labeling
ingredients are not included in the US? economic analysis of that rule excludkd for OTC sunscreen drug products no\<,
and added to the monograph by May 21. redesign costs for all OTC drug products includes fewer words than the previous
200 1, products containing these not marketed under current WA’s or language and the final rule contains a
ingredients would need to be current final monographs, explaining number of labeling modifications for
reformulated to replace the that the agency would attribute all products used on small areas of the face
nonmonograph ingredient with a redesign costs associated with future (which are usually marketed in small
monograph ingredient. or the product final monographs to each final size packages). this rule is not expected
must be removed from the market. monograph rule as it published. Alj to require manufacturers to increase the
B. Number of Products Affected redesign costs for this final sunscreen package size or available labeling space.
monograph therefore are attributed to (Although costs of redesigning labels for
Based on data from FD,A’s Drug thii rule alone. future final monographs Were excluded
Listing System. the agency estimates from FDA’s analysis of its OTC drug
that there are approximately 2.800 OTC Approximately 12.000 sunscreen drug
sunscr$eh drug products (different SKU’s will have to be relabel& within product labeling rule. costs for
formulations, not including products a 2:year !mplementation period to . increased package siti were cOr&~
that diff& only by color) and, about comply with the labeling requirements in the analysis of impacts for that
12.000 individual stockkeeping units of this final rule. In addition. regulation (64 FR 13254 at 13283)).
(SKU’s) (individual products, packages, approxititely 550 suntanning SKU’s FDA estimated the cost of &es& by
and sizes). AI1 of the SKU’s will need to will have to be.relabeied within ti 12- counting only the value of the Iabel-
be relabeled, some will require new SPE: month impltimentation $&iod. (As . y&i% that would be lost; after adje. ..__.‘- _..___
testing. and those products lacking noted previo.usly. FDA could not, for the ler?gth of the traditional labeling
approved active ingredients will need to estimate &e number ?f cosmetic cycle. The regulatory cost was .
be reformulated to stay on the market. pr+u$. that contain a sunscreen f&r a calculated as the product of the-number
In addition, certain suntanning nontherapeutic use and that include the of SKU’s. the nuniber of yeais of
products and certain cosmetic products word “sunscreen” or similar terms. in labeling life lost, and the value of each -
containing sunscreens will have to be product labeling. The agency believes, . year of labeling life lost (see 64 FR
. relabeled. As FDA’s Drug Listing Syste‘m . however; the relabeling of thii group of, 13254 at 13278 through’13284).2
does not include suntanning produc& cosm&ic products will impose a Table 1 in section VIII-C of thii --
the agency used-1995 data from A. C. minimal economic burden because. document details FDA’s estimates of the
Nielsen. a recognized p,rovider of market some of these products already include distribution of relab$ii ~o~ts.TesultiRg
data; to estimate that afiproximately 550 the required labeiing. and most : from the final tile. A weighted average
suntanning SKU’s wilI be affected.by tianufacturers revise these labels for cost to redesign a label ofS5.210 per
the labeling. requirements of this mie. marketing .cansi$erations more SKU was used to calculate&e
New labels will also be needed for frequently than fhe allowed 2-year relabelingcostofsunscreen drug
cosmetic products that contain a phase-in period. Therefore. the agency’s products. whereas a weighted average
sunscreen for a nontherapeutic use and estimates do not include a cyst for cost of $6.620 per SKU was used to
that include the word “sunscreen” or relabeling those products that contain calculate the cost of relabeling
similar terms in product labeliogg; The sunscreens for a nontherapeufic, ., suntanning prodticts. A detail4
agency is unable to ideritify the numb& nonphysiol?gic use.) description of the cost analysis is on file
of these cosmetic products, but does not Frequent. labeling redesigns &re a with the Docket Management Bmnch
believe that there are a large number of recognized cost of doing busin- in the (Ref. 47). As ihown. the to&
SKU’sin this category. OTC drug industj. particularly for incremental cost to relabel the
drug-cosmetic and seasonal products. approxititely 12.000 sunsaeen ‘drug
C. Cyst to Relabel ‘Thus. SJ$J’s with labels that would SKU’s is about S1.5 million. whUe the
The relabeling costs for this rule will normally be redvigned within the cost to relabel the approximat$y 550
: . de moderated to the extent that implementation periods were assumed suntanning SKU’s wasabout S1.8
manufacturers codrdinate labeling to incur no additional costs. The cost .fbr million. The greater per SKU cost for
changes for the final sunscreen the remaining SKU’s was calcula&d as. relabeling suntanning products reflecss
monograph with labeling changes the lost value of the remaining life-years the shorter, 12-month,.phase-in’pefiod-
required by the recent rule establishing of the existing label design. FDA With a shorter phase-in perriod?
uniform format and content for OTC estimates that labeling for the majority manufacturers are less.able to
drug product.labeling (64 FR 13254). (90 percent) of the SKU’s affected by incorporate labeling changes into
These costs are not discussed in this this final rule are redesigned at least .voluntary redesign c@&s and. therrfcire.
analysis. however, because ihey are every 2 years. Of the remaining SKU’s, lose label inventory,, -
TABLE I.--ONE-TIME COST TO RELABEL SUNSCREEN AND SUNTANNING SKU’s ($)’
I. .. . . , ..
,. Type of,.Product
..,,_;. :“~ __ ,^,,” ^ I, _ .I. / 1 ),.
Size of Company 0”s : Suntanning Total Cost

Small1 ,649,283 1.128.700 1.777.983

LMathematIcally the foIlowIng formula was used where: N. - number qf SKU’s with labeling life d x
to calculate the incremental relabeling costs: x = life of labeling In years (2.3. oc 6) years. and
&Xl. - XJ N.A.(l/w). where j P L to (x-y) y = phase-In period In years A. - amortized annual value of labeltrig with a
Total Cost, - Cost* + Cost,, + cost,* ure of x years.
Federal ‘Register/ Vol. 64. No. 98 /Friday. May 21, 1999 /Rules and Regulations 27685

The one comment that raised not been tested using the monograph resistant or very water resistant) and
economic issues in response to the SPF t.estmethod. However, the SPF test SPF factor tested, and ranges from
tentative final mqnograph expressed method inthis document is essentially $2.500 to $6.500. On the assumption
concern about available labeling space the same as the method described in the that 50 percent of the traditional
on small packages of sunscreen drug proposed rule. If manufacturers have . sunscreen drug products. and none of
products. The comment stated that all added new products, made formula’tlon themake-uptypesunscreenpmducts~
text needs to be eonci.se..The agency changes. or otherwise needed to test er make water resistant cla&is..and 50
considered this comment in developing retest the SPF of their products since. p?rCent Of the products that make W&e+
the final rule, which contains specific 1993, they tiould probably have used resistant claims make very water
labeling modifications for small the mast current (i.e.. the ~rcpsed) test resistant claims. the estimated werghted
packages and.for sunscreen products method, Therefore, the agency estimates zyqge cost of the SPF test ls’83.514. . -
used on small-areas of the face (e.g., FDA estimates the total cost of this
lips, nose, ears, and/oraroundthe eyes). that from 15 to 30 percent of the
sunscreen drug products will require requirement, themfore. to’range.from
D. Cost ‘ro Retest SPF ’ retesting as a result of this .document 53-J million to ?%l millions (see the ... .
FDA is &certain about the number of The cost of the .SPFtest varies, .following Table 2).
OTC sunscreen drug products that have depending on the product claim (water
TABLE ~.-ONE-&E COST To RUST ‘$PF ASSUMING 15 PERCENT OR $6. PERCENT C~~~PLIANGE RATES ($)
:
.15 Percent Noncompli- 30 Percent Nowcompli-
8ize of Company .a.rlcf? ante
..
‘.f. ,.. 2600,ooo .-
Small 1,300.ooO
Large. 1.800.000 3.500,ooo
Total Cost /_ii > ^ 3.100.000
. l_“._..,, 6.100800
.
,”
..

E. Cost.to Refomxdate Beca&OTC sunscreen drug products completed for the one ingredient in
are well characterizedtopical these two products or if the two ’
Reformulation costs will depend on formulations,~FDA estimates the cost to . products are removed from the market.
the number of produets. if any, that will reformulate,at about $350.000 per the cost of reformulation would be ..
have no active ingredients ‘with. product Thus, on the asstimQtiori that eliminated.
completed USP compendia1 the manufacturer risfon$.rlat& rather
monographs by the end of the ’ C. Small Bushzess Impact .
thgn removes the products fi-om the
implementation period. At the present .market, the.one-time cost of Based on the analysis of FDA’s drug .
time: only two of the active ingredients reformulation for two products would listing system and other data described
being considered do not have a USP be $700.060. prevIously:there are about 180 domestic
monograph. According to the agency’s companies that manufacture OTC
drug listing system, two prod~ts. : F. Total Incremen&l coscS 1 sunscreen and suntanning products.
manufactured by one ‘company contain The estimated total one-time .Distributors were not assigned costs
one of these ingredients. The agency is incremental cost of this rule. using the because manufacturers of OTC drug
not Wrrendy aware ofother products in midpoint of the cost range for retesting products are’usually responsible for
the marketplace that contain these two and reformulation is $8.6 millton (see product labeling. testing, and
ingredients. Table 3 of this document). These formulation. AQQroximately 78 percent
The cost to reformulate a product estimates are.based on 16 of the 18 of these firms meet the Small Business
varies by the nature of the active sunscreen ingredients under Administration’s definition of a small.
reformulation, the type of product, and consideration having USP compendia1 entity for this industry (less than 756
the size and complexity of the company. monographs. If a USP monograph is employees). ’
TABLE ~--TOTAL INCREMENTAL COST TO INDUSTRY ($)

The rule will require manufacturers of arrangements to comply with the and product retesting to be completed.
sunscreens to relabel their products. laperwork and other requirements of The agency found that the savings to
Some firms will need to retest the SPF his rule. industry of delayed implementation
of these products, and one firm may (estimated to be about $845.OOO).were
Ff. AnaJysJs of Alternatives
have fo reformulate or remove two not great enough to justify delaying
products from the market. Because of The agency altered several proposed- appropiiate use and safety information
the 2-year implementation period, most xgulatog provisions to reduce the to consumers of OTC sunscreen drug
fi m will be able Co relabel during a economic burden of this rule on products,
normal relabeling cycle, at no additional tidustry. For example. FDA decre&ed Finally. the agency ls ,brovidiig a 12-
cost. FDA cannot estimate with he amdunt of required labeling-and month implementation period for
certainty the number of small firms that provided small package 1 certain suntanning prem,tions to add
will need to retest or reformulate their %zcommodations for certain products. new waming.inforr+ion. For this
OTC sunscreen products. but projects l%e labeling required by the proposed catego*, consumets may believe that
that from 15 to 30 percent of all rule would.have increased the needed these products are providing sun. * .
products may need to be retested and label and/or package size for. as many as protection when. in fact, they do.not’-- ‘. ..
that 2 products may teed to be 30 percent of the sunscreen products. They may for+0 using other products
reformulated. Costs will va:y by firm, Such se adjustments could have that have been demon&at@ to be .
depending on the type and number of imposed estimated additional one-time effective in providing sun protection. -
products requiring relabeling, retest.in& relabeling costs of $18 million and beli&ing that their tanning product
and reformulation. The firm-specific annually recurring costs of $22 million provides some measure of protection.
impact may vaiy inversely with the (see Eastern Research Group.‘“Cost Because the pew warning for.
volume of product sales, however, [+a& of the Over-the-Counter suntanning preparations presents an
because per unit cO.stswill be lower for’ Phar&cetitical Labeling Rule*.’ (Ref. important safety issue that needs to be
products with high.volume sales. Thus, 48)). Also, in response to .the comment conveyed to consumers at th;e .earliest
the relative economic impact.of product (see section ILH. comment 32 of thii possible date, the agency Fnsideted
retesting or relabeling may be greater for document). the agency has xecotisidered requiring a.6-month iniplementation
small firms than for large firms. its position on SPF testing of water period forthese products. However.
Because of the 2-year phase-in period.. resistant and very water resistant given the s&asonal nature of these
allowed for sunscreen drug and drug- productsand eliminated the static test products, the agency was concerned that
cosmetic products. which allows requi?ement for these priiducts. As the some manufacturers may not have
manufacturers the flexibility to average cost of the static test is sufficient time to incorporate the
incorporate regulatory changes with approximately $2.800. the estimated labeling change without disrupting theti
voluiltary/markeI-driven changes, the savings to industry due’ to the productiori schedules, By providing an
eeconomic impact of the relabeling elimination of thii test-is about additional 6 months to implement the
requirement is relatively low $7$0,ooo. change. compliance costs were tiuced
(appfoximately $3.3 million). However, The agency a&o considered a number by $1.8 million. . .
for those small companies that may ‘of implementation alternatives to this
have to relabel a substantial number of final ruIe. Generally, the agen* allows VIII. Paperwork l&iuction Act of 1995
products, the out-oPpocket costs could only a l-year implementation peritid for FDA concludes that the labeling
be significant. final monographs. However. because requirements in this document z&e not’
Also. the cost to a small company most sunscreen products are produced subject to review by the Office of
needing to reformulate a product. seasonally, the 2-year period Will Management and Budget because they .’
estimated at approximately $350.000 substantially enhance the ability of the do not constitute a “col@ctio~ of
would be signif’icant. This impact may industry tq relabel and reformulate its information” under the Paperwork 2
be moderated by other options available, products, if necessary. and sell its Reduction Ati of 1995 (44 US-C. 3501
which may be more cost effective than- existing~@roduct invkntories. The 2-year et seq.). Rather. thelabeling statements
i-eformulation. For example. a period will also allow sunscreen are a “public disclosure of Mformation
manufacturer may be able to substitute manufacturers to coordinate the originally supplied by the Federal
other formulations. shift production to a required labeling changes with routine government to the recipient for the
contrkt manufacturer with an approved industry-initiated labeling changes and purpose of disclosure to the public” (5
formulation. or temporarily remove the changes required by the new OTC drug CFR 1320.3(c)(2)).
product from the market and await the product labeling final rule’ (64 FR
completion of a.USP compendia1 13254). IX. Environmental Impact
monograph for the ingredient. Because A 3-year implementation period for The’agency has determined that under
the OTC drug industry is highly sunscreen drug products was 2 1 CFR 25.31(c) this action is of a type
. regulated, all firms are expected to have considered. but the agency determined that does not individually or
access to the necessary professional that a 2-year period provides sufficient cumulatively have a significant effect on
skiUs on staff or to make contractual time to allow the required relabeling the human environment. Therefore.
Federal Register/ Vol. 64. No. 98/Friday, May 21. 1999 /Rules and Regulations 27687
.. I
neither an environme& assessment IPART 352-SUNSCREEN DRUG (2) Moderate sun protection product.
nor an enviionmental.impact statement PROOUCTS FOR OVER-THE- A sunscreen product that provides an
is required. COUNTER HUMAN USE SPF value of 12 to under 30.
(3) High sun protection product. A
List of Subjects sunscreen product that provides an SPF
Subpart A-General Provisions
21 CFR Part 310 value of 30 or above.
sec. (c) Sunscreen active ingredient. An
Administrative practice and 352.1 Scope.
352.3 Definitions. act&e ingredient listed in $352.10 that
procedure. Drugs. Labeling. Medical absorbs, reflects. or scatters radiation in
devices. Reporting and recordkeeping the UV range at wavelengths from 290
requirements. Subpart B-Active Ingredients ’ to 400 nanometers.
352.10 Sunscreen active ingredients. (d) Sun protection factor (SPF) value.
2I CFR Part 352
352.20 Permitted combinations of active The UV energy required to produce an
Labeling, Over-the-counter drugs. ingredients. MED on protected skin divided by the
LJV energy required to produce an MED
21 CFR Part 700 on unprotected skin, which may also be
Subpart C-Lebeling
Cosmetics, Packaging and containers. defined by the following ratio: SPF.
352.50 P&cipal display panel of all value = MED (protected skin (ps))/MED
21 CFR Part 740 sunscreen dntg products. (unprotected skin (US)). where MZD
352.52 -L&ding of sunscreen drug (PS) is the minimal erythema dose for
Cosmetics. Labeling. *. proflucts. protected skin after application of 2
Therefore, under the Federal Food, 352.60 Labeilng of permitted combinations
of active ingredients. milligtims per square ceritime’ter of the
Drug. and Costietfc Act, arid under fm%l formulation of -the sunscreen- -. ‘-s
authority delegated to the Commissioner product. and MED (US) is t$e minimal
of Fo$d and Drugs, 21 CFR part 352 is Subpart p--Testing Procedures erythema dose for unprotected skin. i.e..
added and 21 CFR parts 310; 700. and 352.70 Standardsticceen. skin to whichno sunscrer+producthas
740 are amendedas follows: 352.7 1 Light source (solar simulator). been applied. in effect, the SPF value in . .
352.72 General testing ptocedur& the reciprocal of the effective
PART 310-NEW DRUGS 352.73 Determination of SPF value. transri&sion of the product viewed as a
352.76 Determination If a product is water W radiation filter.
‘I. The authority citation for 21 CFR resistant or very water resistant.
part 3 10 continues ‘to read as follotis: 352.77 T&t modifications. Subpart B&?iv~ Ingr&i&ts
Authority: 21 U.S.C. 321.331.351.352. Auulodty 21 U.S.C. 321.~51.352.353.
355.360.371. g 35210 Sunscreen active ingredients.
353.355.3605-360f. 36Oji361(a). 371.374.
375.379e: 4’2 USC. 216.241.242(a$262, The active ingredient of the ,product
263b-263n. Subpart A-General Pro&ions consists of any of the following. within
the’?oncentration specif%d for each
. .2. Section 310.545 is amended by 53521 scope. ingredient, tind the frnishecl product
adding paragraph (a)(29). by revi@ng (a) An over-the-counter sunscreen prbvides a minimum SPF value of not
paragraph (d) introductory text, by drug product iqti,fot~~ suitable for less than 2 as measured by the testing.
adding and reserving paragraph (d) (30). topical administration is generally procedures established i” subpqrt q.of
and by adding paragraph (d)(31) to read recognized as safe and effective and is this part:
as follows: nbt misbranded if it meets each (a) Aminobenzotc acid (PAPA) up.&
condition in this part and each general 15 percent..
0 310.545 (Irug products ccntaining cond,itidn established in S 330.1 of this (b) Avobenzone up to 3 penzent. ’
certain active ingiedients offered over-the- c) Cinoxate up to 3 percent.
cgunter (OTC) for cettatn uses. chk$Zferences in this part to td) fReserved].
(a) * * t .r&gulatory sections pf the Code of (e) Dioxybenzone up to 3 percent.
Federal ReguWions are to Chapter I of Homosalate up to 15 percent.
(29) Sunscreen drug products. [Reserved].
: Diethanolamine methoxycinnamate Title 21 unless otherwise noted. Menthyl anthranilate’up’to 5
Digalloy1 trioleate 5352.3 Definifions.
Ethyl 4-(bis(hydroxypro$yl)] aminobenzoate
Clyceryl aminobenzoate Asusedinthispart:
Lawsone with dihydrox@etone (a) Minimal eqthema dose &fED).
The quantity of erythema-effective percent.
Red petmlatum (k) Ott 1salicylate up to 5 percent.
I * * * * energy (expressed as Joules per square (1) Oxygenzone up to.6 percent.
meter) required to produce the first (m) Padimate 0 up to 8 p&-cent.
(d) Any OTC drug product that is not perceptible. rednessreaction with
tn‘compliance with this section is (n) Phenylbenzimidazole sulfonlc
clearly defined borders. acid up to 4 percent.
subject to regulatory action if initially (b) Product category designation
introduced or initially delivered for (0) Sulisbbenzme up to 10 percent.
(PCD). A labeling designation for .(p) Titanium dioxide up to 25 percent.
introduction into interstate commerce sunscreen drug products to aid in (q) Trolamine salicylate up to 12
after the dates specified in paragraphs selecting the type of product best suited percent.
(d) (1) through (d)(3 I) of this section. to an individual’s complexion (r) Zinc. oxide up to 25 percent.
t * * * * (pigmentation) and desired response to
ultraviolet (UV) radiation. 0 352.20 Permitted combinations of active
(30) [Reserved] (1) Minimal sun protection product. A ingredient=
(3.1) May 2 I,2001 for products subject sunscreen product that provides a sun The SPF of any combination product
to paragraph (a)(291 of this section. protection factor (SPF) value of 2,to .is measured by the testing procedures
3. Part 352 is added to read as follows: under 12. established in subpart D of this part.
27688 Federal Register/Voi. 64. No. 98/Friday, May 2 1. 1999 /Rules and Reglilations

(a) Combinations ofsunscreen active Sunscreen product testing prockdures in “minimum”) “protection against”
ingredients. (I) Two or more sunscreen § 352.76):. (select one of the following: “sunburn”
active ingredients identified in (c) For products that satisfy the very or “sunburn and tanning”)], or “(bullet]
§ 352.10(a). (c). (e). (6. and (h) through water resistant sunscreen product for skin that sunburns minimally”.
(r) may be combined with each other in testing procedures in 9352.76. (1) (ii) Forproducts that provide an SPF
a single product when used in the “Very” (select one of the following: of 12 to under 30. Select one or both of
concentrations established For each “Water. ‘* “Water/Sweat.” or “Water/ the following: [“(bullet]” (select one of
ingredient in § 352.10. The Perspiration’:) “Resistant.” the following: “provides moderate” QP -_
concentration of each active ingredient (2) “SPF (insert SPF value of the “moderate”)-“p>otection against”<select
must be sufficient to contribute a product, as stated in paragraph (a)(l) or one of the followina: “sunburn” or
minimum SPF of not less than 2 to the (a)(2) of this section, after it has been “sunburn and tannyng”)]. or “[bullet] for.
finished product. The finished product tested using the very water resistant skin that sunburns easily”.
must have a minimum SPF of not less sunscreen product &sting procedures in (iii) For produca that provide an SPF
than the number of sunscreen active S 352.76):. of 30 or above. Select one or both of the
ingredients used in the combination following. [“[bullet]” (select one of the
935252 Lab,etin& of sunscreen drug
muttiplikd by 2. following “provides high” or “high’*).
(2) Two or more sunscreen active product&
“protection against*’ (select one of .@e
ingredients identified in 5 352.10(b). (c). (a) Statement ofidentity. The ltibeling following: “sunbuni” ‘or “sunburn and
(4. Q. (0 through 0. (0). and (ql may of the product contains the established tanning”)], or .?[bullet’) for skin highly . .J
be combined with each other in a single name of the drug. if any, and identifies sensitive to sunburn’*.
product when used in the the roduct as a “sunscreen.” (c) Warnings. The labeling of the
concentrations established for e&h (by Indications. The labeling of the product contains the following w&rnings
ingredient in 5 352.10. The product states, under‘the heading’ under the heading “Warnings:‘*
concentration of each active ingredient “Uses,” all of the phrases IistedJn -(L) Forprodticrs containing any, ’ ;
must be sufficient to contribute a paragraph (b)(l) of this section that are ingredient in 5352.10. (i) “When using
minimum SPF of’n& LessX~ti 2 to ilie appliczbie to the.product and may this pfoduct [bullet] keep out ofeye& .- ;
fmished procjuct.‘The finished product contain any of the additional phra,xs Rinse with water to reniove.”
must have a minimum SPF of not less lilted iq paragraph (b)(2) of this section, (ii) “Stop use and ask-a doctor if
than the number of sunscreen active as appropriate. Other truthful and [bullet] rash or irritation develops and
ingredients used in the combination nonini+zading statements, describing lasts”.
multiplied by 2. only the uses that have been established (2) For produ& con&n& any
(b) [Reserved]. and &ted in this paragraph (b). may ingnxiient identi&d in S352.10
(c) [Reserved]. also be used, as provided in 5330.1 (c) (2) marketed as a l&&i&. The external use
of this chapter. stibject to the provisions only wamirig in S 201.66(c)(5)(i) of this
Subpart&LabeIin$ of section 502 of the act relating to chapter and the warning in pa&grapii .
misbranding and the prohibition iti (c)(I)(i) of this section are nbt require&
5 35250 Pri&i&f d?spltiy panel of ttll sectioil30 1(d) of the act against the (ci) iX-+fOns. The l+eiing of .the
sunscreen drug products. introduction or delivery for introduction Product contains the foIlowing .
In gddition to the statement of into interstate commerce of unapproved statements, as appropriate, under the
identity required in s352.52. the. new drugs in violation of se&on 505(a) heading “Directions.” More detail@
following labeling statements shall be of the act. directions applicable to a particular
prominkntly placed on the principal (1) For prqducts con&ining any product fonpulation (e.g.. cream. gel.
display panel: ingredfentin§352.10. (i) “[bullet]’ lotion, oil. spray, etc.) may also be
(a) For products that do.not satis& the helps prevent sunbum.(bullet] higher included.
water resistant or very water resistant. ._ SPF gives m&e sunburn protection”. (1) For products containing any
sunscreen ptvaucc .te.sung procedures in (ii) For products *at satisfy the water ingredent in § 352. IO. (i) “[bullet] . .
§ 352,76. (1) For pmducts with SPF :resistant testingprocedbres identifM in apply” (select one or more of the
V&N$S up to 30. “SPF (insert tested SPF 5352.76. “[bullet] retains SPF after 40. followin& as applicable: “liberally.”
value of the. product up to 30):’ minutes of’ (select one or more of the “generously.” “~moothly.“~or “evenly’*) :.
(2) For products wi@ SPF values ov?r following: “activity in the water,” “(insert appiopriate time interval, if a ..
30. “SPF 30” (select one of the “sweating.” or “perspiring”). waiting period is needed) before sun
following: “plus” or “+“). Any (iii) For products that satisfy the very ex osure and as needed”.
statement accompanying the marketed water resistant testing procedures Pii) “[bullet] children under.6 months
product that states a specific SPF value identified in 5352.76. “[bullet] retains of a e: ask a doctor”.
above 30 or similar language indicating SPF after 80 minutes of’ (select one br (4 In addition to the directions
a person cari stay in the sun more than more of the following: “activity in the provided in § 352.52(d)(l). the following
30 times longer than without sunscreen water.” “sweating.” br “perspiring”). may be used for products containing’
will cause the prod&t to be misbranded (2) ,Addftional indications. In addltfdn ‘any ingredient in 8352. IO. “[bullet]
under section 502 of the Federal Food. to the indications provided in paragraph reapply as needed or after towel drying,
Drug. and Cosmetic Act (the act). (b)(l) of this section, the following may swimming. or” (select one of the
(b) For products that satisfy the water be used for products containing any following: “sweating” or “perspiring”).
resistant sunscreen product testing in redient in S 352.10: (3) If the additional directions
procedures in 5352.76. (1) (Select-one of 7i) For products that provide an SPF provided in §35252(d)(Z) are used. the .
the following: “Water,” “Water/Sweat,” of 2 to under 12. Select one or both of .phrase “and as needed” in
or “Water/Perspiration”) “Resistant.” thd.following: (“[bullet]” (select one of 8 352.52(d) (1) is not required.
(2) “SPF (insert SPF value of the the following: “provides minimal.” (4) For products marketed as a
product. as stated in paragraph (a)( 1) or “provides minimum.” “minimal.” or lipstick. The directions in. paragraphs
(a)(2) of this section. after it has been (d)(l) and (d)(2) of this section are not
tested using the water resistant ‘See 5 20 I.GG(b)(4) of this chapter. required.
Federal Register-1 Vol. 64. NO. 98/Friday, May 21. 1999/Rules and Regulations
27689
(e) Statement on product
performance-( 1) For products “Warnings” states: “Keep out of eyes.”
(1) In addition. the labeling of the
containing any ingredient identified in and “Stop use if skin rash occurs.”
product may contain any of the “other
5 352.10. the following PCD labeling (v) The warning ir. § 20 I .66(c) (5) (x) of
this chapter may be limited to the allowable statements” that are identified
C/alms may be used under the heading in the applicable monographs.
following: “Keep out of reach of
“Other information” or anywhere children.” (2) For permitted combinations
outside of the “Drug Facts” box or
(vi) For a lipstick, the warnings “Keep containing a sunscreen and a skin
enclosure.
out of eyes” in §352.52(f)(l)(iv) and protectant identified in 5352.20(b).
(i) For products containing active “Keep out of reach of children” in
ingredient(s) that provide an SPF value (c) Warnings. The labeling of the
5 35252(f)(i)(v) and the directions in
of 2 to under f 2. (Select one of the § 352.52(d) may be omitted. product states, under the heading
following: “minimal” or “minimum”) (2) The labeling shall he printed in “Warnings.” the warning(s) for each
“sun protection product.” accordance with the requirements of ingredient in the combination, as
(ii) For products containing active § 201.66(d) of this chapter except that established in the warnings section of
ingredient(s) that provide an SPF value any requirements related to the applicable OTC drug monographs.
of 12 to under 30. “moderate sun §26UX(c)(l). (c)(3). and (c)(7). and the For permitted combinations containing
protection product.” horizonta!. b&lines and hairlines a sunscreen and a skin protectant
(iii) For products containing active described in §2OLSS(d)(S), may be ‘. identified in § 352.2061).
ingredient(s) that pmvide an SPF value omitted. (d) Directions The labeling of the
of 30 or above. “high sun protection
product: § 36260 Labeling of permitted product states. under the.heading
combinations of active ingredients. “Directions.” directions’that conform to -
@I For products containing any the directions established for each
h?gredientYdentff?ed in 8352. IO, the .Statements of identity. indications,’
folio wing labeling statement may be warnings. and directions for use. ingredient in the directions sectionsof. --
used under the h.eading ‘Other respectively, applicable ‘to each the applicab!e OTC drug monographs.
-
information ’ or anywhere outside of the ingredient intbe product may be
l
unless otherwise’ stated in this*
“Drug Facts” box or iwclosure. Y&n combined to eliminate duplicative paragraph. When the time intervalsor .- _
a1ert.zLimiting sun exposure, wearing words or phrases so that the resulting’ age Iimitations for administration of the
protective clothing, and using . information is. clear and understandable. individual ingredients differ, the
sunscreens may reduce the risks of skin (a) Statement of identity. For a directions for the combination product
aging. skin cancer, and othei.harmful combination drug product that has an may not contain any dosage that
effects of the suq.” Anyvariation of this established name: the labeling of the exceeds those established for any
statement ‘will cause the product to be product states .tbe established name of .individual ingredient in the ap&abIe
misbranded under section502 of the the combination drug product, followed OTC drug monograph(s). and may. riot
act. by the statement of identify for tich provide for use by any age group lower
Q Products labeled for use onv on ingredient in the combination, as than the highest minimum age limit
specific small.areas of the face (e.g., established in the statement of identity established for any individual
-* sections of the applicable OTC drug
lips. nose. ears. and/oratound eyes) .’ ingredient:For permitted combinations
and that meet the criteria estabhshed in monographs. For a combination drug containing a sunscreen and a skin
§201.66(d)(lO) of this’chapter. The title product that does not have an : protectant identified in §352.2O(b).
headings. subheadings, and information’ established name, the labeling of fhe
described in § 20 1.66(c) of this chapter product states the statement of identity Subpart D-Testing Procedures
shall be printed in accordance with the for each ingredient In the combination,
+ established in the statement of g352.70 Standard sunscreen. -
following specifications:
(1) The labeling shai1 meet the identity Sections of t&applicable -OTC (a) Laboratory validation. A standard
requ$rements of 5 20 1.66(c) of this drug monographs. sunscreen shall be used con&nit&&y
chapter except that the title. headings, 0 Indkations. The labeling of the in the testing procedures for
and information described in product states. under the heading determining the SPF value of a
§201.66(~)(1). (c)(3). and (c)(7) may be. “Uses.” the indication(s) for each
ingredient in the combination & sunscreen drug product to ensure the
omitted, and the headings, subheadings, uniform evaluation of sunscreen drug
and information described in established in the indications &&ions
920166(c)(2), (c)(4). (c)(5). and (c)(6) of the applicable OTC drug monographs, products. The standard sunscreen shall
unless otherwise stat& in this be an 8-percent homosalate preparation
may be presented as follows: with a mean SPF value of 4.47 (standard
(i) The active ingredients paragraph. Other truthful’and
nonmisleading statements. describing deviation = 1.279). In order for the SPF
(!Z201.66(c)(2) of this chapter) shall be determination of a testproduct to be
listed in alphabetical order. only the.indications.for use that have
. been estabhshed in the applicable OTC considered valid. theSPF of the
(ii) The heading and the indication standard sunscreen.must fall within the
required by § 20 I .66(c) (4) may be drug monographs or listed in this
paragraph (b). may also be used. as standard deviation range of the expected
Iimited to: “Use [in boid type] helps
prevent sunburn.” provided by § 330.1(c)(2) of this chapter, SPF (i.e., 4.47 + 1.279) and the 95-
subject to the provIsions of section 502 percent confidence interval for the mean
(iii) The “external use only” warning SPF must contain the value 4.
in § 201.66(c) (5) (i) of this chapter may of the Federal Food, Drug,, and Cosmetic
be omitted.
Act (the act) relating to misbranding and (b) Preparation of the standard
the prohibition in section 301(d) of the ‘homosalate sunscreen. (1) The standard
(iv) The subheadings in act agatnst the introduction or dellvixy
S 201.66(c)(5)(iii) through (c)(5)(vii) of homosalate sunscreen is prepared from
this chapter may be omitted. provided for introduction into interstate two different preparations (preparation
commerce of unapproved new drugs in A and preparation B) with the following
the information after the heading violation of section 505(a) of the act. compositions:
27690 Federal Register/ Vol. 64, No. 98 /Friday. May 21. 1999 /Rules. .-, and
.’ ,. Regulations

COMPOSITION OF PREPARATION A AND PREPARATION B OF THE STANDARD SUNSCREEN

(2) Preparation A and preparation B (51 Calculation of the concentratioi of Skin Tp and $mbum &xi Tanning History
are heated separately to 77 to 82 *C. ht%osalate. The concentration of fBased on fist 30 to 45 minutes sun exposure
witli constant stirring. untik the contents homosalate is determined by the after a winter season of no sun exposure.)
of each part are solubiliti. Add following fcjrmula which takes into [-Always burns easily. never tans
preparation A slowly Q pr&paration B (sensitive).
consideration the absorbance of the lI--Always tiu?ns easily; &ns
whi!e stirring. Continue stirring untii sample of the test solution, the dilution (sensitiye). _. minis~&ly ’
the emulsion formed is cooled to room of the l-percent solutior~ (1:50). the l’ff-Burns moderately: w gradtialiy’(Iight
temperature (15 to 30 “C) . Ahd sufficient weight of the sample of the standard brown) (normal).
purified water to obtain 100 grams of homosalate sunscieen preparation fl.. .. -- tV--Burns minimally always-tans we@-- - -- -. ,.
standard sunscreen preparation. gram), ,and the standard absorbance @noderate brown) (normal).
(c) Assay of the standard homosdate value (172) of homo&late asdetermined V-Lately bums: tans profusely iiark brown) ..
sunscreen. Assay the standard’ . (Insensitive).
homosalate sunscreen preparation by by ave?ging the absorbance of a large VI-Never bums: deeply pigmented
the following method to ensure proper number of batdhes of raw homosalate: (insensitive).
concentration: Concentration of homosalate = (2) A medical history shall be
(1) Preparaclon of th~gssaysolvent. absorbance x 50 x 100 x 172 = percent obtained from all subjects wit$~.
Tht: solvent consists of,1 percent glacial concentration by weight. emphasis on the effects of sunlight on
acetic acid (V/V) in denatured ethanol. their skin. Ascertain the gener,al health
The denatured ethtiol should’& 9352.71 Light sour& (solar simulator). of the individual, the individual’s skin
contain a UV radiation absorbing A solar simulator used for type Q. II. or 1I.l), wheth.er the’ individual
denaturant. determining the SPF of a suns&en d&g is taking medication (topical or
(2) Preparation of a lqercentsolution pioduct should be filtered so that .it systemic) that is known to produce
of the standard homosalate sunscreen provides a continuous emission abnormal sunlight responses. and
preparation. Accurately weigh 1 gram of spectrum from 290 to 400 nanotietersi whether the individuai is subject to any
the standard homqsalate sunsixeen abnormal responses to sunlight. such as -
similar to sunlight at sea level from the
preparation into a 100-milliliter sun at a zenith angle of 10 P; It has less a photototic or photoallergic response.
volum.etric flask. Add 50 milliliters of than 1 percent of its total energy output (b) Test site inspection. The phy&al
the assay solvent. Heat on a steam bath examination shall determine the
contributed by nonsol~.wavelengths presence,of sunburn, suntan. scars. :
acd mix well. Coql the solutloti to room shorter than 29Onanometers: and ft’ has
temperature (15 to 30 “C). Then dilute active dermal lesions. and uneveri ikin
the sdlution to voltime with the assay ,not more than 5 tiercent of its to@1 tones on the areas of the back to be
. solvent and mix well to make a l- ener& output cqntributed by tested. The presence of nevi. blemishes.
percent solution. wavelengths longer than 400 or moles will be acceptable if in the
(3) Preparation of the test solution nanometers. In addition, a solar physician’s judgment they wtll not
(150 dilution of the 1-percent solution). simulator should have-no sign&ant interfere with the study results. Excess
FiIter a portion of the J-percent solution time-related fluctuations in radiation hair on the back is acceptable if &he hair
through number 1 filter paper. Discard emissions after .an appropriate warmup is clipped or shaved.
the first 10 to 15 .milliliters of the time, and it should have good beam (c) Informed consent Legally effective
filtrate. Collect the next 20 milliliters of uniformity (within 10 percent) in the written informed consent niust be
the filtrate (second collection). Add 1 exposure plane. To ensure that the solar obtained from all individuals.
milliliter of thesecond coIl&ccion of the simulatoi delivers the appropriate (d) Test site delineation-( 1) Test site
filtrate to a 50-milliliter voIumetric spectrum of UV radiation. it must be area. A test site area serves as an area
flask. Dilute this solution to volume measured periodically with an for determining the subject’s MED after
with assay solvent and mix well. This accurately-calibrated spectroradiometer application of either the sunscreen
is the test solution (I:50 dilution of the system or equivalent instrument. standard or the test sunscreen product.
I -percent solution). !j 352.72 General testing procedures.
or for determining the subjedt’s MED
(4) Spectrophotometric determination. when theskin is unprotected (control
The absorbance of the test solution is (a) Selection oF test subjects (male and kite). The area tq be tested shall be the
measured in a suitable double beam female). (1) Only fair-skin subjects with back between the beltllne and the
spectrophotomeeer with the assay skin types I. II. and III using the shoulder blade (scapulae) and lateral to
solvent and reference beam at a following guidelines shall be selected: the midline. Each test site area for
wavelength near 306 nanometers: Selection of Fair-skin SubJects ‘applying a product or the standard
Federal Register/ Vol. 64, No. 98 /Friday, May 2 1. 1999 /Rules and Regulations 27691

sunscreen shall be a miniinum of 50- be exposed to the varying doses of UV fluorescent light bulb that provides a
square centimeters. e.g:. 5 x LO radiation in a randomized manner. level of illumination at the test site
centimeters. The test site areas are (fl Waiting period. Before exposing within the range of 450 to 550 lux. and
outlined with ink. tf the person is to be the test site areas after applying a the test subject should be in the same
tested in an upright position. the lines product. a waiting period of at least 15 position used when the test site was
shall be drawn on the skin with the minutes is required. irradiated. Testing depends upon
subject upright. If the subject is to be (9, Number ofsubjects. A test panel determining the smallest dose of energy
tested while prone. the markings shalI shall consist of not more than 25 that produces redness reaching the
be made with the subject prone. subjects with the number fixed in borders of the exposure site ae 22 to 24
(2) Test subsite area. Each test site advance by the investigator. Frond this hours postexposure for each series of
area shall be divided into at least three panel. at least 20 subjects must produce exposures. To determine the MED.
test subsite areas that are at-least 1 valid data for analysis. somewhat more intense erythemas must
square centimeter.. Usually four or five (h) Response criteria. In order that the also be produced. The goal is to have
subsites are employed. Each test subsite person who evaluates the MED some exposures that produce absolutely
within a test site area is subjected to a responses does not know which no effect. and of those exposures thaf
speclfi&i dosage of UV radiation, in a sunscreen formulation was applied to produce an effect. the maximal &xp.osure
series of UV radiation exposures. in which siteor what doses of W should be no more than twice the total
which the test site area is exposed for radi&tion’were admiiistered. h&lie eneigy of the minima1 exposure.
the determination of the MED. must riot be the same person who (i) Rejection of test data. Test data
applied the sunscreen drug product to shall’ be iejected if the exposure series
(e) Appl&ation of test nkteriafs. To the test site or administered the doses of
ensure standardize,d reporting and-to fails to elicit an MED response on.either
W radia&ion. AfteFW radiation the treated or unprotected s&n s&es. or
define a product’s SPF value. the exposure from the solar simulator is .e
afiplication of the product shall be if the reponses on the treated sit- are
completed. all immediate responses randomly absent (which indicates the
‘&pressed on a weight basis per unit shall be recorded. These include several
area which establishes a standard film.
product was not spread evenly). or if the
iypes of typica! responses such as the subject was noncompliant (e.g.. subject .
Both the test sunscreen product and the following: An immediatk darkening or
standard sunscreen application shall be withdraw? from the test due to illness
tanning, typically greyish or.purpliih.in or work conflicts, Subject does not
2 milligrams per square centimeter. For color. fadii in 30 to 60 minutes. and
Oils and most lotions. ‘the viscosity shield the exposed testing sites from
is
attributed to photo-oxidation of existing further U-v radiation until the MED is
such that the material canbe applied 9eIanin gr&ules: immediate reddening, .
with. a volumetric syringe. Fdr creams. read. etc.). .
fading rapidly.-andviewed as a normal
heavy gels, and butters,. the product response of capill&-& and venules to s352.73 Determination of SPF value.
shall be warmed slightly so that it can heat visible and infraned &i&ion; and (a) (I) The following erythema action
he applied’volunietrically:. On heating, an immediate generalized heat‘&ponse.’ spectim shall be used to +lculate the
car& shall be taken no{ to alter the .reseinbling prickly heat rash. fading in erythema e@ctive !xpcisure of a solar
product’s physical characteristics. 30 to 60 minutes;and apparently caused ‘simulatoi:
especially separation of the by heat and moisture generally irritating Vi@)- 1.0(250<hc298nm)
formulations. Pastes and ointmen& shall to the skin’s surface. After the
be weighed, then applied by spreading Vi(x)~l.o0~~~-‘)(298<X<3i8
imme@ate responses ace n+d. i&h nanometers)
‘on-the test site area. A product shall be subject shall shield the exposed area
spread by using a finger cot. If two or Vi (AI)E 1.OOnlsCl39* &) (328 .< I < 400
froni f&thq W radiation for the
more sunscreen drug products are being remainder of the test day.The MED Ls. nanometers)
evaluated at the same tinie. the test determiGd 23 to 24 hocus aftet (2) The data contained in’this action
p.roducts and the standard-sunscreen. as exposure. me erythema respons& of spectrum are to be used as spectra!.
specsed in § 352.70. should be applied the test subJect should be evaluated weighting factors to calculate the
ln a. bdnded. randomized ‘manner. If tinder the following conditions: The erythema effective exposure of a sdlar
> only one sunscreen drug product is source of illumination should be either siinulator as follows:
: being tested. the testing subsites should a tungsten tight bulb or a warm white BIUJNG COOE 4160-01-F
27692 Federal Register/Vol. 64, No. 98IFriday. May 21, 1999f R~1e.s and Regulations

MUlUG CODE 4766-01-C
subsite arr on each subject with an produce the, MED of the protect& skin
. (b) Determination of MED ofthe accura~eljr-calibrated so&r simulator. A and from the dose of W radiation .
unprotected skin. A series of W &es of seven exposures shall be required to produce ‘the MED of the
. radiation exposures expressed a&J?uIes administered to the protected test sit& unprotected skip (control site) as
per square meter ‘(adjusted.tq the to,detkmine the ivIED of the protected, follows:
erytheq action spectrum calc~&ted skin .(MED(PS)j. The doses selected SPF value = the ratio of erythema effective
according to § 352.73(a)) is administered shall consist of a geometric series of five exposure Uoules per sqtiare meter) (MED(PS))
to the subsite areas on each subject’ with exposures, where the middle exposure to the erythema e@cUve exposure Uoules per
an accurately caIibrated solar simulator. 6quare meter) (MED(US)). .
is placed to yield the expected SPF plus (dl Determination of the test pcoduk’s
A series of five exp&Ures shall be two otlier exposures placed
adniinistered to the untreated. SPF value and PCD. Use data from at
symmetrically around the middle least 20 test subjects with n representing
unprotected skin to determine thi exposure. The exact series of exposures
subject*% inherent MED. The do&. the number of subjects used. First, for
to b$:given to the protected skin shall each subject compute the SPF value-as
selected shall be a geometric series be determined by the previ+tsly ’
represented by (1.25n). wherein each stated iri S 352.73fb) and (c). Second, .’
established MED(US) and&e expected compute the mean SPF value, k and the
exposure time interval is 25 percent SPF of the test sunscreei~. For products
greater than the P;revious time to standard devktion, s. for these subjects.
with an expected SPF less than 8, @e Third, obtain the upper 5-percent point
maintain the same relative unk-tainey exposures shall be the MED(US) times from the t.d&ribution table with n-l
(expreked as a constant percentage), 0.64X. 0.80X. 0.90X. 1.00X. 1.10X.
j independent of the subjece’s sensiti&zy degrees of freeddm. Denote this value by
1.25X. and 1.56X. where X equals the t. Fourth, compute ts/ dn. Denote this
.Lto UV radiation, regardless of whether expected SPF of the test product. For
the subject has a high of low MED. qua+ty by A (i.e., A = ts/ &). Fifth,
products with an expected SPF between calc&late the SPF value to be used in
Usually, the MED of a person’s 8 and 15. the exposures shall be the
unprotected skin is determtned the day labeling as follotis: the label SPF equals
MED(US) times 0.69X. 0.83X. 0.91X. the largest whole number .less @an k -
prior to testing a product. This MEDQJS) 1.00X. 1.09X. 1.20X. and 1.44X. where
shall be used in the determination of the A. Sixth and last, the drug product is
X equals the expected SPF of the test classified into a PCD as follows: if 30 .t
series of UV radiation exposures to be product: For product+ tiith an expected
administered to the protected site in AckthePCDisHigii:ifi2+A<ic
SPF greater that 15. the exposures shall < 30 + A. the PCD Is’Moderate: if 2 +
subsequent testing. The MEDO be the MED(US) times 0.76X. 0.87X. A < 2 < 12 4 A. the PCD is Minimal:
should be determined again on the same 0.93X. 1.00X. 1.07X. 1.15X. and 1.32X. if %-z 2 4 A. the product shall not be
day as the standard and test sunscreens where X equals the expected SPF of the labeled as a sunscreen .drug product and
and thk MED(US) should be used in test product. The MED is the quantity of shall not display an SPF value.
calculating the SPF. erythema-effective energy required to
(c) Determination of individual SPF produce the first perceptibfe. §3!j2.76 Determination if a product is
values. A series of UV radiation unambiguous redness reaction with water resistant or very water resistant.
exposures expressed as Joules per clearly .defined borders at 22 to 24 hours The general testing procedures in
square meter (adjusted to the erythema postexposure. The SPF value bf the test 5 352.72 shall be used as pati of the
action spectrum calculated according to sunscreen is then calculated from the following tests, except where modified
§ 352.73(a)) is administered to the dose of UV radiation required to In this section. An indoor fresh water
Federal Register/ Vol. 64, No. 98/Friday. May 2 I, 1999 /Rules and Regulations 27693

pool. whirlpool. and/or jacuzzi used. Any proposed modification or conspicuously at least once in the
maintained at 23 to 32 PC shall he used alternative procedure shall be submitted labeling in conjunction with the term
in these testing procedures. Fresh water as a petition in accord with § 10.30 of “sunscreen” or other similar sun
is clean drinking water that meets the this chapter. The petition should protection terminology used in the
standards in 40 CFR part i4 I. The pool contain data to support the modification labeling. For example: “Contains a
and air temperature and the relative or data demonstrating that an alternative sunscreen-to protect product color.”
humidity shall be recorded. procedure provides results of equivalent
(a) Procedure for testing the water accuracy. All information submitted PART 740-COSMETlC PRODUCT
resistance oFa sunscreen product. For will be.subject to the disclosure rules in WARNING STATEMENTS
sunscreen products making the claim of part 20 of this chapter. 6. The authority citation for 2 1 CFR
“water resistant.” the label SPF shall be
the label SPF value determined after 40 PART 700-GENERAL part 740 continues to read as follows:
minutes of water immersion using the Authority: 21 U.S.C.321.331.352.355,
4. The authority citation for 21 CFR 36 1.362.37 1,374.
following procedure for the water part 700 continues to read as follows:
resistance test: 7. Section 740.19 is added to subpart
(1) Apply sunscreen product Aulhorityr 21 U.S.C. 321.331.352.355. B to read as foliows:
(followed by the waiting period after 361.362.371.374.
application of the sunscreen product 5. Section’7O.O.35is added to subpzirt 5740.19 Suntanning preparations. .
indicated on the prod&& labeling). B to read’as follows: The labeling of suntantiing
(2) 20 minutes moderate activity in preparations that do not contain a
water. 5700.35 Cosmetics containfrig sunscreen sunscreen ingredient mtist display the
(3) 2O-minute rest per& (do not ingredient+. following warning: “Warning-mis
towel test sit&). (a) A ljroduct that includes the term product does not contain a suqcreen
(4) 20 minutes moderate activity iti “sunscreen” in its labeling or in any and does not prot&t’against sunb&n.
;water. bther way represents or suggests that it Repeated exposuieof unprotected&in
(5) Conclude water test (air dry test is intended to prevent, cure. treat, or while tanning may increase the risk of
sites without toweIing). mitigate disease or tp affect a structure Skin aging. skin cancer, and other -
(6) Begin solar siniulator exposure toor function of the body cOmestiithin harmful effects to the skin even if yc~u ’
the definition qf a drug in section
test s.ite areas as described in 5 352.73. do not burn.” For purpwes of this
20 I @( 1) of the act. Sunscreen ac@ve
(b) Procedure for testing a ‘veIy water section. the term “suntanning
resistant sunscreen product. For ingredients affect the structure oi preparations” includes gels. creams.
sunscreen products making the claim of function of the body by absorbing. liquids. and other typical products that
“very water resistant,” the label SPF reflecting. or scattering the htil, are intended to provide coSmetic effects
shall be the label SPF v$lue determined burning rays of the suti thereby altering on the skin while tanning through.
after 80 minutes of water immersion the normal physiok&ical response to exposure to W radiation (e.g...
using the foIlowing procedure for the solar radiation. These ingredients also moisturizing or conditioning products).
very watei resistarit test: he!p tb prevent diseases such as or to give the appearance df a tan by
(1) Apply sunscreen product sunburn and may reduce the chance of imparting color to the skin through the
(folIowed by the waiting per&i after premature skin aging, skiri cancer, and. application of approved color additives
application of the sunscreen pm+.tct other harmful effects due to the sun (e.g.. dihydroxyacetone) without the
indicated on the product labeling). when used in conjunction with limiting need for exposure eo W radiation. The
(2) 20 minutes moderate activity in sun exposure and wearing protective term “suntanning preparations” does
water. clothing. When consumers see the term. not include products intended to
(3). 20-minute rest period (do not “sunscreen” or similar sun protection provide sun protection or.otherwise
towel test sites). terminology in the labeling of a product. intended to affect the structure or any
‘w$Lr20 minutes moderate activity in they expect the product to protect them
in some way ftom the harmful effects of function of the body.
(5) i&minute rest period (do.not the sun. irrespective of other labeling Datedz’April22.1999.
toweltest sites). statements. Consequently, the use of the Wiiiam K.-Hubbard.
(6) 20 minutes moderate activity in t&m “su~creen” or similar sun Associate Commissioner for Policy
water. protection terminology in a product’s Coordination.
(7) 20-minute rest period (do not labeling generally causes the product to [FR Doe. 99-12853 Filed s-20-99: 8~45am]
towel test sites). be subject to regulation as a drug. BIIUNG COOE 41&01-F
(8) 20 minutes mod&ate activity in However, sunscreen ingredients may
water. also be used in some products for
(9) Conclude water tesr (air dry,test nontherapeutic. nonphysiologic uses DEPARTMENT OF DEFENSE
sites without toweling). (e.g., as a,color additive or to protect +e
(IO) Begin solar simulator exposure to color of the product). To avoid Office of the Secret&r/
test site areas as described in 8 352.73. consumer misunderstanding. if a
cosinetic product contains a sunscreen 32 CFR Part 311
QX52.77 Test modifications. ingredient and uses the term
The formuIation or mode of “sunscreen” or similar sun protection OS0 Privacy Program: Correction
administration of certain products may terminology anywhere in its labeling. AGENCY:Department of Defense.
require modification of the testing the term must he qualified by describing JCT~ON: Final rule: correction.
procedures in this subpart. In addition,’ the cosmetic benefit provided by the
alternative methods (Including sunscreen ingredient. SUMMARY:This rules makes
automated or in vitro procedures) (b) The qualifying information administrative corrections to the OSD
employing the same basic procedur& as required under paragraph (a) of this Privacy Program rule published on
those described in this subpart may be section shall appear prominently and April 28, 1999.

-
hgs ?r devices under
h Service Act, there is
.y and a person who is
10 specific provision of
omulgated under such
er in controversy, the CHAPTER VI-COSMETICS
trocedure under which
iy request a review, df ADULTERATED COSMETICS
appropriate scientific.
m advisory committee. SEC. 601. (3611 A cosmetic shall be deemed to be adulter-
Sew shall take plack- ated-,
lmulgate such r@$%L-.. (a) If it bears or contains any poiSonous or deleterious sub-
Tent of the Food and’: stance which mtiy render it injurious to users under the conditions
. .,Jy *of use prescribed in the labeling thereof, or, under such conditions
...$
.... of use as are customary or usual; except that this provision shall
cls. not apply to coal-tar hair dye, the label of which bears the folloti.-
application or submi&; ing legend conspicuously displayed thereon: “Ctiution-This pro?-
ry other similar form i uct contains ingredients which may cause skin irritation on certain
submit a request tA Y individuals and a preliminary test according to accompanying di-
le product as a drug :’ rections should first. be made. This ‘p&u& must not be used for.
-duct sub’ect to s*: dyeing the eyelashes or eyebrows; to do so may cause blindness.“,
! Food an d Drug P and the labeling of whiti bears adequate directions for such pre-
n+submitting the I liminary testing. For the purposes of this paragraph and paragraph
@on for the pxodu (e) ‘the tern-i “hair dye” shall not inchide eyelash dyes or ‘eyebrow
opxiate. dyes.
@k the receipt of the (b) If it consists in whole or in part of any filthy, putrid. or-de-
ary shall determine’: composed substance.
m (a!, or the compoi Y% (4 If it has been prepared, packed, or held under insanitary
at Ml regulate f&e ‘.
tten statement that. conditions ‘whereby it may have become contaminated with filth, or
It, and the reasons .’ whereby it may have been rendered injurious to health.
modify such state- (d)‘If its container is composed, in whole or in part, of any poi-.
erson, or for public sonous or deleterious substance which may render the contents in-
jurious to .health.
does not provide (e) If it is not a hair dye and it is, or it bears or contains, a
7 in subsection‘(b) color additive which is unsafe within the meaning of section 721(a).
subsection (a) shall) MISBRANDEj? COSMETICS
? secretary of su&
: of the Food and . SEC. 602. C3621 A costietic shall. be deemed to be mis-
duct, as applicable branded- - - ’
‘t with the writted’ (a) If its ,labeling is false or misleading in any particular.
sons based on‘sci- (b) If in package form unless it bears a label containing (1) the
name and place of business of the manufacturer, packer, or dis-
tributor; and (2) an. accurate statement of the quantity of the con-
tents. in terms of weight, measure, or numerical count: Provided,
That under clause (2) of this paragraph reasonable variations shall
be permitted, and exemptions as to small packages shall be estab-
lished, by regulations prescribed by the Secretary.
(cl If any word, statement, or other information required by or
under authority of this Act to appear on the label or labeling is not
prominently placed thereon with such ,.conspicuousness (as com-
pared with other words, statements, designs, or devices in the la-
beling) and in such terms as to render it likely to be read and un-
255
derstood by the ordinary individual under customary conditions of
purchase and use.
(d) If its container is so made, formed, or filled as to be &’
leading..
!ey-If it is-a color additive, unless its packaging and label&~.
are !n conformrty w&h such packaging and labeling requiroments&
apphcable to such color additive, as may be contained in wt?: CHI
tions issued under section 721. This araeranh shall nnt SUBCW=‘T
packages of color additives which, wit R re- ___ _
metics, are .market&l and intended for use=onl
(as definedin the last sentence of section 60i(a iy1 ---- -
(0 .rf its packaging or labeling is in violation of an appli&Z s&. 7(ji. ‘2
regulakon issued pursuant to section 3 or 4 of the Poison for the efficient
tidn Packaging Act of 1970. ” :q+.,, vided in thiss%
09 The SC’
,REG&TIONS MAKING EXEMPTiOk~ ; 2yjs and Human Sq. ..
SECT 603. [363] ‘Ihe, Secretary shall promulFat* +e&lafiil cient enforceme
exempkng from any ‘labeling re+irement of t&- ---- W’LUb. wise provid&$
which are, .in ar;cordanoe 6th the practice -of the-trade to L+ such manner 8~ ,.
essed, ‘labeled, or repacked in substantial quantities it estabhsh*~ Secretary of Be
ments other than those where originally processed or packed,%$$
condition that such cosmetics are not adulterated or misbrandGIW%?
under the provisions .of this Act upon removal from .such pro&sS$~~~
ing, labeling, or repacking establishment. . ?..I:;:
.,,.d
:$$A

order entere
~ifl be adve
-.
261 FEDERAL FOOD. DRUG, AN0 COSMETICACT Sec. 704
-
- The Secretary shall.
s of such documents. to conduct or cause to be conducted, such research as may be re-
g nature of the docu-‘. quired.
K all guidance doe*- (e) Any officer or employee of the Department designa.ted by
rments. the Secretary to conduct examinations, .investigations, or mspec-
: tions under this Act relating to counterfeit drugs may, when so au-
pmn$s+oner, shalll; thorized by the Secretary-
enodlcally in the tl) carry firearms;
d I such documents ,. (2) execute and serve search warrants and arrest war-
.:.. rants;
55ve appeals me&a-j; .; (3) execute seizure by process issued pursuant to libel
I Food and Drug Ad:!’ Y under section 304;
zce documents in ac- .:.;: (4) make arrests without warrant. for offenses under this
Act with respect to such drugs if the. offense is comm+ted m
his presence or; in the case of a felonjr, if he has probable cause
to believe that the person so arrested has committed, or IS corn-
mitting, such offensi?; and
(5) make, prior to the institution of libel proceedings ~uxi+r.
section 304(aX2), seizures of hgs or containers or of*equlq-
m&t, puncks, dies, plates; stones, lab$ing,.or’ other things, If
they are, or he has reasonable grounds to believe that they aie,
subjkt to seiztie and condemnation under such se+ion
304(a)(2), In the event of seizure +sIiant to t+is, ,arap?p$ ,.
G) 1, libel proceedings under section 304(aX2). shal P be ms!l-
tuted promptly and the .property seized be placed under the Ju-
risdiction of the court.
RECORDS ‘OF IN’i’ERSTATE StiIPMENT. ’

SEC. 703. i3733 For the p&pose of enforcing the provisions ‘of.
this Act, carriers en ged in interstate commerce, and p.ersoris ye-
&king food, drugs, r evices, or cosmetics in ix$erstate commerce or
holding Sudh articles so received, shall, upon the request of an ofTi-
cer’ or etiployee duly designated by the Secretary, permit such of%
cer or employee, at reasonable times, to have access t.~ tid to copy .’
all records showing the movement m interstate commerce Of any
food, drug, device, or bosmetic, or the holding thereof dun?g or
after such movement, and the quaptity, shipper, and consignee
thereof; and it shall be unlawful for any -such carrier or person to
fail to ermit such access to and copying of any such record so ye-
queste dpwhen such request is‘accompanied ljy a statement in wnt-
ing specifying the nature or&i&d of food, dru , device, or cosmetic
to which such request relates, except that evi.8 ence obtamed under
this section or any evidence which is directly or indirectly derived
wr& of any. a&;; fi-om such’kvidence, sh&ll not be used in a .criminal prosecution of
:’ .;<.
the person from whom obtained, and except that .carriers shall not
wxutive branch of: ..-;.. be subject to the other provisions of this Act bi reason-of ,th$r re-
any offxcia2’ of -the: ‘. ceipt, ‘carriage, holding, or delivery of food, drugs, devices, or cos-
nake such inspec:.: : :>I;.. metics in the usual course of business as can’iers.’
::,?$;
ed, upon requesi’ FACTORY INSPECTION
and complete. in- ’
:todrugs’as the - SEC. 704. [374] (al(l). lkor purposes of enforcement of this Act,
; application. The offkers or employees duly desiginated by the Secretary, upon pre-
i;.
my such request,- .j,
I Pmbably should be “MS paragraph”,
,,., ..;:*
.I,
Sec. 704 FEOERALFOOO, DRUG. AN0 COSMETICACT 262 263 I

senting appropriate credentials and ti written notice to the owner, (B) prac
operator, or agent in charge, are authorized (A) to enter, at reason- drugs, or pn
able times, any factory, warehouse, or establishment in which food smanufacturc
drugs, devices, or cosmetics are manufactured, processed, packed’ or manufacl
or held, for introduction into interstate commerce or after such in: of their prof
troduction, or to enter any vehicle, being used to transport or hold (C) . pe
such food, drugs, devices, or cosmetics in interstate commerce; and compound, 4
03) to inspect, at reasonable times and within reasonable limits solely for u
and in a reasonable manner! such factory, warehouse, establish- not for sale:
ment, or vehicle and all pertinent equipment, finished and unfin- (D) SIR+
ished materials, containers, and labeling therein. In the case of’any regulation f
factory, warehouse, establishment, or c,onsulting laboratory in .: finding .
which prescription drugs, nonprescription drugs intended for ._.+:. accord&e+,thL3
human use, or restricted devices are manufactured, processed, :...::; of the pubE .’
.packed, or held, inspection shall extend to aU things therein (in- .;.:: ..../
. (3) An-offi;
eluding records, filos,. papers., processes, controls, and facilities) graph (1) for p?
bearing on whether prescriptron drugs, nonpres&ption drugs in- - -*‘- applicable to i.6 :‘ :.
tended for human use, or restricted devices which am adult&rated times, to h&e 6
r or misbranded within the meaning of this Act, or which may not (A) &.
be manufactured, introduced into interstate commerce, or sold or or held in4 .
offered for sale by reason of any provision of this Act, have b’&en _.-.___‘. . tion 412, bi
or are being manufactured, processed, pticked, transported, or held 1’ (B) =ki
in any such place, or otherwise be@ng on violation of this Act. No -+;- (b) upon &-.
inspection authorized, by the preceding sentence or by paragraph “‘T ‘house, consult
(3) shall extend to financial data, sales data other than shipment leaving the p&
data, pricing data, personnel data (other than data as ‘to qualiii&- shall give to tI_
trons of technical and professional. personnel performing functions * ::&, writing sew.
subject to this Act), sxrd research data (other than data relating to z which, in his j$
new drugs, antibiotic drugs, and devices and subjet to reporting .::T metic in such:+
and inspection under regulations lawfully issued pursuant to set- -I filthy, putrid&
tion 505(i) or (k) 1 section 519, or 520(g),. and data relating to other i;. acked, or he%
drugs or devices which in the case of a neti drug would be subject - Eecome conta3
to reporting or inspection under law&l regulations issued pursuant i, dered injurio4
to section 505(j)). A separate notice shall be given for each such in- promptly to thf
spection, but a notice shall not be required for each entry made ’ .::f- (c) If the jj
during the period covered by the inspection. Each such ‘inspection ..i factory, w* -
shall be commenced and completed with-reasonable promptness. .$!I ple in the coy
(2) The provisions of the/.secon$ .sentence of paragraph (1) shall ; .z tion and ptiO$i
not apply to- operator, or q.
(A) pharmacies which maintain establishments in conform- .. $- tained
ante with any applicable local laws regulating the nractice of i 2 (d) Wheng
pharmacy and medicine and which a& regui&y &gaged in or other eStal?f
dispensing prescription drugs or~evices, upon prescriptions of packed, the: di
practitioners licensed to administer such drugs or devices to, sample of anx
patients under the care of such practitioners in the course of for tlie p.urPo$
their professional practice, and which do not, either through a or in part Of a.
subsidiary or otherwise, manufacture, prepare, propagate, erwise unfit 9
compound, or process drugs or devices for sale other than in be fkrnished i
the regular course of their business of dispensing or selling tin(zzy’-’
drugs or devices at retail;
records shall;? ..
‘Probably should read kction 505(i) or (k),“. See the amendment made by section the Secreq
lWbX2XL) of Public Law L@-LL~. times ,tb have.
CHAPTER V-DRUGS AND DEVICES
SUBCHAPTER A-DRUGS AND DEVICES
ADULTERATED DRUGS AND DEVICES
SEC. 501. $3511 4 drug or device shall be deemed to be adul-
terated-
(a)(l) If-it consists in whole or in .part of any filthy, putrid, or
decomposed substance; or (2XA) if it has been prepared, ‘packed, or
held under insanitary conditions whereby it may have been con- ’
taminqted with filth, or whereby it may have been rendered injuri-
ous to health; or (B) if it is a drng.and the methods used in, or the.
facilities or’controls used for;its manufacture, .processing, packing,
or holding .do not conform to or are not operated or administered
in conformity with current good manufacturing practke to assure
that such dn+g meets the requirements of this Act as to safety and
has the idontlty and s.trength, and meets the, quality and purity
characteristics, which it purports. or is -represented to possess; or
(Cl if it is a compounded positron’emission tomography drug and
the methods used in, or the facilities and controls used for, its
compounding, processing, packing, or holding do not conform to -or
are not operated or administered in conformity with the positron
emission tomography compounding standards and the oficial
monographs of the United’ States Pharmacopoeia to assurk that
such drug meets the requirements of this.Act .as to safety and has
the identity and strength; and meets the quality and purity charac-
teristics, that it. purports or is represented to possess; or (3) if its
container is composed, in whole or in part, of any poisonous or del-
eterious substance which may’ render .the contents. injurious to
health; or (4) if (A) it bears or conk&s, for purposes of coloring
only, a color additive which is unsafe’within the meaning of section
721(a), or (B) it is a color additive the intended use of which, in or
oh. drugs or devices is for purposes. of coloring only and is unsafe
within the meaning of section-721(a); or (5) if it is a new animal
drug tihich is unsafe within the meaning of section 512; or”(6) if
it is an ,animal feed bearing: or containing a new animal drug, and
such animal ‘feed is unsafe within the meaning of section 5 12.
(b) If it purports to be or is represented as a drug the name
of which is recognized in an official compendium, and its strength’
differs .from, or its quality or purity falls below, the standards set
forth in such compendium. Such determination’ as to strength,
quality, or purity shall be made in accordance with the tests or
methods of assay set forth in such conipendium, except that when-
ever tests or methods of assay have not been prescribed in such
compendium, or such tests or methods of assay as are’ prescribed
are, in the judgment of the Secretary, insufficient for the making
of such determination, the Secretary shall bring such fact to the at-
91
‘R Ch. I (4-l-00 Edltt&) 5 Food and DNg Administration, HHS g211.1
~.<‘.
*
leans: PART 21 l-CURRENT GOOD MAN- 211.111 Time limitations on production.
211.113 Control ol microbiological contam .i-
tration of the drug siz:’ UFACTURtNG PRACTICE FOR FIN- nation.
ample, weightlweight, :I: ISHEDPHARMACEUTICALS 211.115 Reproccessing.
or unit dose/volume&~
5.....g Subpart A-General Provistcns Subpart G-Packaglng and Labeling
ICY, that is, the the* control
of the drug product., Sec.
211.1 scope. 211.122 M&&LIs examfnation and usage
appropriate laborat&, 211.3 DefinitioLls. criteria.
squately developed and 2ll.l25 Labelmg issuance.
.ca.l data (expkes83ea.t subpart &-0rganImtkan an Id Personnat _--_--_ Paclfedn~
211.1!%0 - __ I _ and labelins - owXati0~.
_
ma of units by refereye 21L22 Responsibilities: of quality control 3llJ32 ‘Famperwvfdent paaksging rewfre-
; unit. .. ments for over-theoopnter (OTC) human
xl yield means the II& 21135 Personnel quahfioations. drug products..
211.28 Personnel reapon@lities. 2ki24 Drug prodact inspeotion. ” :
1 be produced at a&& 2lLl.37 Expirationdatl4r.
$ of man&&ura, pa ‘211.34 ccnsultants. ._
lug of a particular.& subpcurH--HdQlgclnd-
upon the qnantl%~:~
be used, in the absen 211.42 Deaf& and construction features. 2ll.142 Warehousing procedures.
211.44 Llshtin2.. ‘.; ;2l$l50 Distribution
.._ - .,.:.: procedures.
error in actual prog~ .
211,46VentfMlon. air flltratipn, .ah he+&.
andoooling.
ield means the &I~SI 211.43 Plumbing.
g produced at any 211.50 Se-e andrkuse. -’ 2ll.160 &neralrequirements.
211.32 Wsshingand toilet faoilities. 2ll.hj3 &&ing and relezwe for distribution.
qf manllfaetur6,
211.56 sanitation. -211.136 Stability test@&
cing of a particular 2D.167 special tegtlng requirements. 1
211.53 Maintenance.
: 211.170 Reserve samples.
2ll.173 -LaboratoLy animak.
211.176 Penicillin contamination. _- .
21.63 Equipment design, size, and location.
211.65 EQtlipment cons.truction. Subpart J+ccr& and Repok
211.61 Equipment c&aning and main*
nanoe. 211.160’ &eral requirements. .
2lLr33 Atitititii, mechanical. &l eleo- 2U.182 .J3quipment cleadw and use log.
trohfc eqtlfpmeat. Pill84 Component. drug prodnct container.
211.72 Filters, :* :; ‘5’ clospre. and Jab(illng record%
>ii.iss. Ma&ter production and control
subpart er,,i,l ot compollents.clird’: -** i :
Drug Product &&lners and -fir . zn1.188. hatch production and control
wqds.
Iwqds.
2ll.30 General requirements. 2lu.92Q2 l-mduction
pl-lxhlotion recoti
i!ecol!d red3w.
ied3w.
211.32 Receipt and etorage of untested corn- .2D194 _- ---
-mtoW m&torYrecords.
racorda
ponents. drug product oontainers. .and 3ll.19696 Distribution
Distribution records..
records..
closures. . . ..
w.y3 ea Complaint
Complaint file&
filea
211.64 Testins and aptikl or rejkction of
coniponen~, dmg‘ product c6nta$ner$ s&&t K+tetumttut salvaged DW
aud o1osures. .-‘.
211.66 Use of approped componid :drW
pmduct containers; and closures. .+. .,.. . : 211.204 ~ketarnea~prod~Cta.
2llAT R&estfng~ of appm.ved com*ngntS, 211.208 Drag pr&i~t’salva&nG
drug product containers. @.ndclosures.
’ 211.33 Refected components. drug produdt ADTBORITP: ir U.S.C. 33l.331, 3% 3% 36ob.
containers, and closures. : 371.374. .’
211.94 Drug product oontalners and closures. i3mi~0~: 43 FR 43377.Sept. 2% l!% unh=’
.otherwise noted.
subport F-Prod&d2 and Process
-.
Subparf A-Generqt PrOViSiOn$
211.1M) Written procedure& deviations.
211.101 Charge-in of components. 6ill.l. scope.
spt, 29, ‘1978.as amended 211.103 Calc6lat~oq of yield. ‘. (a) The r&ulations In this part Con-
, lS6& 56 FR 41353.Aug. 3. 211.103 Equipment identifloatlon. :
211.110 Sampling and testfng of in-prooess’ $&I the minimum current good manu-
materials and drug products. facturing practice for preparation of

115
’

*21 CFRch.:l(4-1kO Edition) kood and Drug ,Ad&lsfrpHon, HHS. 9211.42
$211.3
occurred, that they ,have. been .fully in- and supervise the manufaoture, proc- (6) Any such building shall have ade-
drug produots for administration to hu- easing, packing, or holding of eaoh drug puate space for the orderly placement
mans or animals. vestigated,, The. quaJity control unit 9;
shall be responsible for approving or re-. product. of equipment and mate&d8 to prevent
(b) The current good manufacturing mixups between different components,
practice regulations in this ohapter, as jetting drug produots manufactured, ,021X38 Pereonqe! respon&.litiss.
processed,’ paoked, or .held, under con- drug produot containers, closures, la-
they pertain to drug products, and in (a) Personnel engaged m the manu- beling, in-process materials, or drug
parts 600 through 680of this chapter, as &sot by another company..
(b) Adequate. laboratory facilities for facture, process,ing; packing, or holding produots, and to prevent contamina-
they pertain to biologiCa products for of a. drug product .shall wear,, clean tion. The flow of components, drug
human use, shall be considered to sup- the testing and approval (or rejection)
plement, not supersede, the regulations of oomponenta, drug product oon- olothing appropriate for the . duties product dontainers. closures, labeling,
tainers, olosures, paokaging materials, they perform, Protective apparel, such in-prooess materials, and drug products
in this part unless the regulations ex- as head, face, hand, and arm, ooverings,
plicitly provide otherwise. In the event in-process materials, and drug produots through the building or building8 shall
it is impossible to comply with applica- shall be available to the quality con- shall be worn as necessary to protect be designed to prevent contamination.
trol unit. drug prod&s from contamination. (c) Operations shall be performed
ble regulations both in this part and in
other parts of this chapter or in parts (c) The quality .control unit shall @) Per8oMel shall practice go.od within speoiflcally defined areas of ade-
600through 680of this chapter, the reg- have the responsibility for approving sanitation and health habits. iluate size. There Shall be separate or
ulation specifically applicable to the or rejeoting all prooedures or specifica- (0) Only personnel authorized by su- defined areas or such other.oontrol sys-
drug product in question shall super- tions impacting on the identity, pervisory per8onnel shall enter those terns for the flrm’s operations as are
sede the regulation in this part. strength, quality,. and purity of the areaa of : the buil’dings and faCilitie8. necessary to prevent contamination or
(c) Pending consideration of a pro- drug product. designated as 1imited;aooess areas. mixups during the course of the fol-
nosed exemotion. oublished in the FED- (d) The responsibilities and’ proce- * W hY ~l%‘SOhShOWnat W fh’ne (ei- lowing procedures:
ERALREGISTERof September 29, 1978, dures applicable to the quality control ther by .medioal examination or super- (1) Receipt, Identification, storage,
the requirements in this part shall not unit shall.be In writing; such written ’ visory observation) to have an appar- and withholding from use of oompo-
procedures shall be followed. ent lllne88 or open lesions that may’ad-
be enforced for OTC drug products if
the products and all their ingredients vereely affeot. the safety or quality of nents, drug product containers, clo-
are ordinarily marketed and consumed 0 211.25 P&o&e1 qualifications; drug.produots shall be excluded from sures, and labeling, pending the appro-
as human foods, and which products (a) Each person engaged in the manu- direct contact wit+ components, drug priate sampling, testing, or examina-
product containers, olosures, in-process tion by the quality control unit before
may also fall within the legal deflni- facture, processing, packing, or holding
tion of drugs by virtue of their in- of a drug.product shall have education, material8, and drug produots until the release for manufacturing or pack-
tended use. Therefore, until further no- training, and experience, or any com- COnChtiOn is correoted or determined by’ aging;
oompetent medical personnel not to (2) Holding rejected’ component&
‘iice. regulations under part 110 of this bination thereof, to ‘enable that person drug product
chapter, and where applicable, parts 113 to perform the assigned functions. jeopardize t;tze8asetY Or quamy of drug labeling beforecontainers
~spositi;n. closures, and
to 129 of this chatter. shall be aDDlied Training shall be in the Particular OP- produots. All ‘personnel shall be ‘in-
eratioaa that the employee performs struoted to report to sup.ervisory per- (S) Storage of released ‘components
in determining whether these OTC-drug
products that.are also foods are manu- and in current good manufacturing Wmel any health conditions that may drug product containers, closures, and
factured, processed, packed, or held practice (Including the current good. have an adverse effect on drug. prod- labeling;
under current good manufacturing manufaoturing pradtice dregulations in uota. (4) Storage of in-process materials;
practice. this.ohapter and :svr.ttten procedures re- (5) Manufacturing and processing op
9iil.34 consultants.‘~ erations:
[43FR 45077,Sept. 29,1978,as amendedat 62 quired by these regulations’) a8 they re:
late to the emproyee’s functions.. .. C)ons&ants advising on the m&u; (6) Packaging and labeling .oper-
FR 66522, Dec.19.1997) fscture, processing, ‘packing, or holding ations;
Training “in current ‘good manufac-
9 211.3 Definitions. turing praotlce shall be’ conducted by of drug. produots shall have suffioient (7) Quarantine storage before release
qualified individuals on a. continuing education, traitig, and, experience, or of drug products;
l’he definitions set forth in $210.3 of basis and with suffloient’ frequency to any combination thereof, to advise on (8) Storage of drug products after re-
this chapter apply in this part. assure that employee8 remain familiar the subject for which they are retained. lease;
.with CAMP requirements applicable to Reoords shall be maintained stating (9) Control and laboratory oper-
Subpart B--Organization and them, the name, address, and qualifioations ations;
. Personnel (b) Each person responsible for super- OF any consultants and the’ type. of (10) Aseptic processing, which ‘in-
vising the. manufaoture, processing, service they provide. cludes as appropriate:
$211.22 Responsibilities of quality packing, or holding of a drug product (f) Floors, walls, and ceilings of
control unit. shall have the education. training. and Subpart 6-hIdings and Facilities smooth, hard surfaces that are easily
(a) There shall be a quality control experience, or any combination there- cleanable;
unit that shall have the responsibility of, to petform assigned funotions in Q211$esDe&p and construotion fea- (ii) .Temperature and humidity con-
and. authority to approve or reject all such a manner as to provide sssurance . trols:
,.. -.---
components, drug product containers, that the drug produot has the safety, WI AnY m.ilcUng or buildings used in
closures, in-process materials, pack- identity, strength, quality, and purity the manufacture, processing, paokfng, high-efficiency nn.r).i~tr’
aging material, labeling, and drug that it purports or is represented to or holding of a drug produot zhali be of under positive pressure, regardless of
products, and the authority to review possess. suitable size, construotion and looation whether flow is laminar dr nonlamfnar;
production records to assure that no (c) There shall be an adequate ‘num- to faoflitate cleaning,. mafntenanoe, (iv) A _system
errors have occurred or. if errors have her of aualifiad aaraanne~ to nfwfmm I and nroner onrrrakf nna -;-A-* __ 1.1. for monitoring environ-
‘I
i .*.
.

21 CF,RCh: I (4-i -00 Edltlon) Food and, Dtig ,Ad&Isfratfon, tiH.S 9’211.8:
$211.72
(c) Ragged or boxed oomponents of (1) The dontainers of oomponents se- the .manufacturer and provided tha
record of the program shall be main- lected shall be cleaned ,,where nec- the manufacturer establishes the’reli
tained along with appropriate valida- drug produot oontainers, or olosures
shall be stored off the floor and suit-’ essary, by appropriate means.. ability of the supplier’s test result.
tion data. Hard copy or alternative sYs- (2) The containers shall. be opened, .thrgugh appropriate validation. of the
terns, such as duplicates, tapes, or ably sp,aced to permit oleaning .and in-
speotion.. satipled, and resealed in ‘& manzier de- eupplier’s test results at appropriate
microfilm, designed to assure that signed;.to prevent cdntamination of intervals,
backup data are exact and complete (d) Each container or grouping of
containers for components or drug their oontentg ,.,=a oontamination of (4) When appropriate, component:
and that it is secure from alteration, other..oomponents, drug .Droduct ooq- shall be microscopically examined.
inadvertent erasures, or loss shall be produot containers, or closures shall be
identified with. a distinctive code for tainers, or~oldsures. (5) .Each lot of a component, drug
maintained. (3) Sterile equipment ana aseptic product container, or closure that iz
each lot in each ‘shipment received..
’ [43FR 45077.Sept. 39.1978.as amendedat 60 This code shall be used in recording the sampling teohniques shall be used when liable to contamination with filth, in-
FR 4091,Jan. 20.19951 disposition of each lot: Each lot shall heoessary. sect infestation, or other extraneou:
be appropriately identified as to its (4) If it is necessary to sample a oom- adulterant shall be examined against
$211.72 Filters. status (Le., quarantined, approved, or ponent from the top, middle,’ and hot; established specifications for such con-
” Filters for liquid filtration used in rejected). tom of its container, suoh sample sub- tamination.
the manufacture, processing, or pack- divisfons shall not‘ be oomDosited for (6) Eaoh lot of a component, drug
ing of injectable drug products in- g211.82 Reoei~t and storage of untest- teetlng. I* * - product container, or closure that is
tended for human use shall not release ed component+ drug product con- (6) Sample ‘oontafners shall be’identi- 1fabl.e to microbiological contamina-
fibers into such products. Fiber-releas- tainers, and closured; fled so’ that the following fnformation tion that is oblectlonable in view of iti
ing filters may not be used in the man- (a) Upon reieipt an6 before acoept- oan .be determined: :name’ of the mate- intended use shall be subjected to
ufacture, processing, or packing of an&, eaoh container or grouping of rial sampled, the lot?number, the con- mfcrobfologioal tests’before use.
these injectable drug products unless it containers of .components, drug prod- tamer from which the sample was
is not Dossible to maaufaoture such uct containers,, and closures shall be .,taken; the date on which the. sample uot(a)containers, Any lot of components, drug prod-
drug products without the use of such examined visually for appropriate la- was taken, and the ntiarof the person the appropriate orwritten closwes that meets
specifications
filters. If use of a fiber-releasing filter beling as to contents, container dam- who oollected tpe. scynple.
(6) Containe.rst from which samples rity of .identity. strength, quality, and pu-
is necessary, an additional non-fiber- age or broken seals, and odntamina- and related tests tider paragraph
releasing filter of 0.22 micron max- tion. have been taken shall be marked to
imum mean porosity (0.45 micron if the (b) Components, drug product con- show that samples. have been removed (d) of this section may be approved and
from ‘them. . released for use. Any lot-of such mate-
manufacturing conditions so dictate) tainers, and closures shall be stored
shall subsequently be used to reduce under quarantine until they have been (a).. Samples .shali b8 examined and rial that does not meet such specifica-
tions shall ‘be rejected.
the content of particles in the tested or examfned,,as appropriate, and tested asfollows: .’
injectable drug product. Use of an as- released. Storage within the area shall ’ (1) At least one test ‘shall bs con- 143FR 45011.Sept.29,197'8.a*;amendedat 63
bestos-containing filter, with or with- conform to the requirements of §211.80, ducted to verifv the id&tits of each. FR 14356.Mar. 25.lOOB]
out eubsequent use of a specific non- oomDohent ‘of a- drug produoc. Specific
fiber-releasing filter, is permissible 0211.84 . Testing and approval or re ec- identity tests, if they exist, shall be 0211.86’ Use of approved’ components,
only upon submission of proof to the tion Of componenta, drug pro dpot ‘used. drug product containers; and clo-
confainem, and closures. ,(2) Each oomponent shall be ‘tested sures.
appropriate bureau of the Food and
Drug Administration that use of a non- (a) Each lot of components, drug for. conformity with all aDpropriate Components, drug prdauct oon-
fiber-releasing filter will, or is likely product containers, and closures, shall written specifications. ‘for purity, tamers. and olosures approved for use
to, compromise the safety or effective- be withheld from use until the lot has .strength, and ._ quality. In lieu of such shall be rotated so that the oldest ap-
ness of the injectable drug product. I been sampled, tested, or examined, as testmg by the manufaoturer. a report proved; @took is used. first. Dev-fatfon
appropriate, and released for use by the of analysis may ‘be accepted from the from thfs requirement is permitted if
Subpart E-Control of Compo- quality control unit. supplier of a oomponent, provided.that such deviation is temporary a.na appro-
(b) Representative samples of each at least. one specific identity test is priate,
nenfs and Drug Product Con- shipment of each lot shall be collected conduoted on suoh component .by the
tainers and Closures for testing. or examination. The num- manufacturer, and provided that the 8211.87 Retesting of approved compc-
ber of containers to be sampled, and manufacturer establishes the reli- nenta, drug product containers. and
821L-80 General requirements. the amount of material to be taken ability of the supplier’s analyses ClONlWS.
(a) There ‘shall be written procedures from each container, shall be based through appropriate validation of the Components, drug product con-
describing in sufficient detail the re- upon appropriate criteria suoh as sta- supplier’s test results, .at appropriate tainers, and closures shall be retested
ceigt, identification, storage, handling, -tistioal criteria for component varia- intervals. or reexamined, as appropriate, for iden-
sampling, testing, and approval or re- bility, confidence levels,’ and degree of (2) Oontitiners and closures shall be tity, strength, quality, and purity. and
jection of components and drug prod- precision desired, the past quality his- tested for conformance with all appro- approved or rejected by the quality
uct. containers and closures; such writ- tory of the supplier, and the quantitjr priate written procedures. In lieu of ‘control unit in accordance with 32lL84
ten procedures shal! be followed. needed. for analysis and reserve where such” testing by the”“manufaoturer, ‘a as necessary, e.g., after storage for
(b) Components and drug product required by 5211.170. certificate of testing may be accepted long periods or after exposure to air,
containers and closures shall at all (c) Samples shal! be collected in ac- from the supplier, protided that at heat or other conditions that mfght ad-
times be handled and stored in a man- oordanoe with the following proce- least :s; vfautil fdentifioation is oon- versely affeot the component, drug
nep f.o nrevent contamination, dures: duoted on such oontalneWclbsurt%s by Droduot contafner, or olosure.
. .
’ !

$211.89 .21 .CFRCh. I (4-I-06 EdBIqn) F&d and Drug Admlnlsfraflon,HkS §211*115
be dooumented st the time of Perform- 0211,106 Equipmb# identiili~tion. of samples shall assure *that the drug
g211.89 Rejected components, drug product and in-process material con-
product .containere, and C~OSUIVS. anoe. Any deviation from the Written ’ (a) All oompounding and storage con-
procedures shall be reoorddfjd and justi- tainers, prooessirig lines,’ and ‘major form to specifications.
Rejected components, drug product (c) In+rocess materials shall’be test-
‘containers, and closures shall be iden- fied. equipment used during the’,produotion
of a batch ‘of a drug product shall be ed for identity, strength, quality, and
tified and controlled under a quar- 0 211.101~ Charge-in of ‘components. purity as appropriate, and approved or
antine system designed to prevent . properly identified at all times to indi-
their use in manufacturing or proc- Written production and’control Pro- cate. their contents and, when nec- rejeoted ‘by the quality ‘control unit,
essing operations for which they are cedures shall ‘include the following, essary, the phase of processing of the ‘during. the production process, e.g., at
unsuitable. whioh are designed to .&sure that the’ batoh. co,mmencement or completion of sig-
drug products produced have the iden- @> Mador equipment shall be identi- nifioant phases or after storage for
Q21k;$Uyug product containers and tity, strength, quality, .and purity they fled- by a distinctive identiffcation long periods.
purport or are represented to possess: number or oode that ‘shall :be reoorded (d) Rejected in-process materials
(a) Drug product containers and clo- (a). The. batch shall be formulated in the batch production record to show shall beIdentified and controlled under
sures shall not be reactive, additive, or with the intent to provide not less than the specific equipment used in the a quarantine system designed to pre-
absorptive so as to alter the safety, manufaoture of each batch of a drug vent their use in manufacturing or
100percent of the labeled or established product. In cases where only one of a
identity, strength, quality, or purity of amount of active ingredient. processing operations for which they
the drug beyond the official or estab- particular type. of equipment exists in are unsuitable.
lished requirements. (b) Oomponents for drug j product a.manufacturing facility, the name of
(b) Container closure systems shall manufacturing shall be weighed, meas- the equipment may be used in lieu of & $ZllJIl Time limitations on produc-
urovide adeouate protection against ured, or subdivided as appropriate. If a dfstfnctive ldentiffcation number or .
ioreseeable external factors in Storage component is removed from the origi- code.
and use that can cause deterioration or nal container to another, the new con- When appropriate, time limits for the
contamination of the drug product. tainer shall be identified with the fol- .completion of each phase of production
(c) Drug product containers and olo- lowing information: shall be established to assure the qual-
sures shall be clean and, where indi- (1) Component name or item code; ity of the drug product. Deviation from
cated by the nature of the drug, steri- (2) Reoeiving or cqntrol number: (a), To assure. batch uiafformity and established time limits may be accept
lized -and processed to remove (8) Weight or measure in new con- ‘integrity of drug products, written pro- able, if such deviation. does not com-
pyrogenic properties ‘to assure that tainer; cedures .shall be established and fol- promise the quality .of the drug prod-
they are suitable for their intended (4) Batch for. whioh component was lowed that dqscrfbe the’ fn~Drcoess con- uot. Such. deviation shall be justified
use. dispensed, including ‘its product name, trols, and tests, or examinations to be and documented.
(d) Standards or specifications, methi conducted on appropriate sa&ples of
cds of testing, and, where indicated, strength, and lot number. in-process ‘materials ,of each batch. 5211.119 Control df microbiologic.al
methods of cleaning. sterilizing, and (c) Weighing, measuring, or subdi- Suoh control procedures shalt be estab- contamination.
processing to remove pyrogenic prop- viding operations for components shall lished to monitor the. output and to
erties shall be written and followed for be adequately supervised. Each con- (a) Appropriate written procedures,
validate the performanoe of those man- designed to prevent objectionable
drug product containers and closures. tainer of component dispensed to man- ufaoturing processes that may be re- microorganisms in drug products not
ufacturing shall be examined by a sec- sponsible for causing variability in the required to be sterile, shall be estab-
Subpart F-Production and ond person to assure that: charaoteristios of in-process material
(1) The component ,.was released by lished and followed.
Process Controls and the drug product. Such control @) Appropriate written procedures,
the quality control unit: 1 procedures shali inolude, but are not designed to prevent microbiological
$211.100 Written procedures; devi- (2) The weight or measure is correct limited to, the following, where apiro-
ations. as stated in the batch production contamination of drug products pur-
priate: ’ porting to be sterile, shall be estab-
(a) There shall be written procedures records: ’ (1) ..Tablet or capsule weight vari-
for production and process control de- ation,; lished and followed. Such procedures
(3) The containers are properly iden- shall include validation of any steri-
signed to assure that the drug products tified. $3)Di$ntegration time;
have the identity, strength, quality, (3) Aaequacy of mixing,to assure uni- lization prooess.
(d) Each component.shall be added to
and p?lrity they purport or are rep- the batch by one person arid verified by formity and homogeneity: 0.211.115 Reprocessing.
resented to, possess. Such procedures a second person. (4) Dissolution time and rate;
shall. include all requirements in this (5) Ularity. completeness,, or pH of so- (a) Written procedures shall be estab-
subpart. These written procedures, in- 8 211.103 Calculation of yield. lutioiis. .lished and followed prescribing a sys-
cluding any changes, shall be drafted, (b) Valid in-prooess specifications for tem for reprocessing batches that do
reviewed, and approved by the appro- ActuaJ yields and peroentages of the- such characteristics shall be consistent not conform to standards or specifica-.
priate organizational units and re- oretical yield shall be determined at with drug product final speoifioations tions and the steps to be taken to in-
viewed and approved by the quality the conclusion of saoh appropriate and shall be .derived from Orevious ac- sure that the .reprocessed batches will
control unit. phase of manufacturing, processing, ceptable process average and process oonforin with all established standards,
(b) Written production and process packaging, or holding of the drug prod- variability estimates: where_....possible specifications, and characteristics.
control procedures shall be followed in uct. Such caloulations shall be per- .
ana aezerminea Dy Gke application of @) Reprocessing shall not be per-
the execution of the various production formed by one person and indepepd- suitable statistical procedures where formed without the review and ap
ahd process control functions and shall ently verified by asecond person. approsnlate. Examination and testing provai of the quality control unit.
1.
:
; .’ . ‘,’

21 CFRCh. l (&1-00 EdItion) F&d and Drug Adn$&ation~ HHS fi211.132
$211,122
(3) Use of visual mspection to con- ~!Ul$?O~ Packaging and IabeIing tip&- and effeotiveness of OTC drug products.
Subpart G--Pa&a ing and An OTU drug product (except a der-
duct a 1Wpercent examination for cor-
Labeling Con7rol reot labeling duiing or after ComPle- There s&l be dvritten’prbcedures de- matological; dentifrice, insulin, or los-
tion of finishing operations for’ ha&- signed to aSsure that correct labels, la- enge product) for retail sale that is not
8211.122 Materials examination and beling, .and packaging materials are packaged in a tamper-resistant paok-
wage criteria. applied labeling. Such 8XaminatiOn age or that is not Properly labeled
used for drug products:, such written
(a) There shall be written procedures shall be performed by one person and procedures shall .be followed. These under this SeCtiOn is adulterated under
. describing in sufficient detail the re- independently verified by a Second Per- prooedures shall incorporate the fol- section 501 of the. act or misbranded
Eeipt, identification, storage, handling, son. lowing features: under section 502 of the act, or both.
sampling, examination, and/or testing (h) Printing devices oh, or aSSOOiated (a) Prevention of mixups and oross- (b) Re~Qfre??x?atslot tamper-evident
of labeling and packag!ng materials: with, manufaoturing ,lines used to im- contamination by ‘physio+l or spatial package, (1) Each manufaoturer and
such written procedures shall be fol- print labeling upon We drug product separation from operations on other packer who packages an OTC drug
lowed. Labeling and packaging mate- unit label or ease shall be monitored to drug products, product (except a d8rmatOlOgiCa1, den-
rials shall be representatively sampled, assure that all imprinting conforms to (b) Identification and handling of tifriO8, insulin, or 1028nge product) for
and examined or tested upon receipt the print epeoified in.the* batch produo- filled drug Droduot containers’that are. retail sale shall package the product in
and before use in packaging or labeling tion reoord. Set aside-&d held, in unlabeled con& a tamper-evident package, if this prod-
of a drug product. tion for future labeling operations to uot is acoessible to the public while
(b) Any labeling or packaging mate- [43 FR 45077,Sept. 29,1078,as amendedat 58 preolude mislab9ling of individual con-. held for’sale. A tamperievident pack-
rials meeting appropriate written SpeC- FR 41555, Aug. 3, lOOS1 q tainers, lots, or portions of lots. Identi- age is one having one or inore indica-
ifications may be approved and re- ficatfon need a& be applied to eaoh in- tore or barriers to entry ivhich, if
leased for use. Any labeling or pa&- ~211.126 Labeling +i.nce.
.divldual container but shall be suffi- breached or missing, can reasonably be
aging materials that do not meet such (a) Strict control shall be exeroisdd oient to determing name, strength, exPected to Drovide visible evidence to
specifications shall be rejected to pre- over labeling Issued for use in drug quantity of oontents, and lot or oontrol co&umers that tampering has oc-
vent their use in operations for which produot labeling operations. number of each container,
they are unsuitable. curred. To reduce the ltkelihood of suc-
(b) Labeling materials issued for a (o).Identific&ipn of ‘the drug product cessful tampering and to increase the
(c) Records shall be maintained for batch shall be carefully examined for with a l.ot or opntrol number that Per- likelihood that consumers will’discover
each shipment received of eaoh dif- identityand conformity to the labeling mits. determination of. the history of if a product has been tampered with,
ferent labeling and packaging material
indicating receipt, examination or specified
duotion
in the master’or batoh pro-
records
the maimfaoture and, control of the the Package is required to. be distino-
batch. . .
testing, and whether accepted or re- tive by design or by the use of one or
jected. (c) Prooedures shall be used to rec- (d) Examination of Pa&aging and la- more indicators or barriers to entry
(d) Labels and other labeling mate- oncile the quantities of labeling issued, beling materials for Suitability and that employ an identifying ohar-
rials for each different drug product, used, and returned, and shall require correctness. before Packaging oper- acteristio (e.g.,. a pattern, name, reg-
strength, dosage form, or quantity of evaluation of discrepanoies found be- ations, and dooumentation of such, ex- istered trademark, logo, or picture).
contents shall be stored separately tween the quantity of drug product fln- amination in the batoh produetion For purPo.ses of this section, the term
record. .’ “distinctive by design” means the
with suitable identification. Access to ished and, the quantity of labeling ‘(e) Inspection of the paokaging and Packaging cannot be duplicated with
the storage area shall be limited to au- issued when suoh disorepanoiea ar9 out labeling facilities fmmediately before commonly
thorized personnel. side narrow preset limits based on his- available materials
(e) Obsolete and outdated labels, la- torical operating data. Such disorep-- use to assure that’ all drug. products through oommonly available proaesse?
beling, and other packaging materials have been removed from previous oper- A tamper-evident package may involve’
an&es shall be investigated in accord- ations. Inspection shall alsobe made to an. immediate-container
shall be destroyed. ance with D211.192.Labeling reoonoili- and closure
(f) Use of gang-printed labeling for ation is w&ived for out or’ roll labeling assure that packaging and labelfng ma- system or secondary-container or car-
different drug products, or different terials not suitable for subsequent op- ton system or any combination of sys-
if a loo-percent examination for correct erations have been removed. Results of tems intended to provide a visual indi-
strengths or net contents of the same labeling’ is performed in accordance
drug product, is prohibited unless the with §211.122(g)(2). inspection shall b8 dOCUm8nted,in the cation of package integrity. The tam-
labeling from gang-printed sheets is batch production records. . per-evident feature shall be designed to
adequately differentiated (d) All excess labeling bearing lot or
by size, control numbers shall be destroyed. 143FR.45077,Sept. 29, 1978,as amendedat 58 and shall remain intact when handled
shape, or color. FR 41554,Aug. S,1993J in
_ a reasonable manner during..--manu-
(g) If cut labeling is used, packaging (e) Returned libeling shall be main- Iaoture, distribution, and retall dis-
and labeling operations shall include tained and stored in n manner to pre- 4211.152 ‘Tkper-evident packaging *lay.
one of the following special control vent mixups and provide proper identi- ‘re uirements for bver-the&ounter (2) In addition to the tamper-evident
fication. I (O&l) human drug products.
procedures: packaging feature described in para-
(1) Dedication of labeling and pack- (f) Procedures’ shall be written de- (a) General. The Food and Drug Ad- graph (b)(l) ‘of this section, any two-
aging lines to each different strength scribing in sufficient detail the control miniStration bar, the authority under piece, hard gelatin capsule covered by
of each different drug product; procedures employed for the issuance the’Federa1 Food, Drug, and Cosmetic this section must be sealed using an ac-
(2) Use of atmropriate electronic or of labeling; such written procedures Act (the aot) to establish anniform na- ceptable tamper-evident technology.
* ele&romechaniEal -equipment to con- shall ba followed. tional requirement for tamper-evident b-9Lube&o. (1) In order to alert con-
, duct a loo-percent examination for cor- paokaging of. OTC drug products that sumers to the specific tamper-evident
rect labeling during or after comple- [43 FR 45077,Sept. 29,1978,as amendedat 58 will improve the security of OTC drug feature(s)’ used, each retail naekapn nf
nmka&,,v a,,A kalt. a--....- ~1-- - .
tion of finishing operations; or FR 41354,Au(l. 9,lQQ31
21 CFRCh. I’ (4-l-00Edition) Food.and Drug Admt.nlstratton,HHS 9211.160
5211.134 ..
OTG drug produots :are required .u.nder (e) Homeopath&o drug produots, shall quirement. is permitted if such devi-
section (except ammonia inhalant in be exempt from the repuirements Iof ation is temporary and appropriate.
crushable glass ampules, containers of 4514.70 of this ohapter .to provide the
ageqoy wi$h notification of ~obwes in .thfs seotion;’ : ‘, @) A system by which the distribu-
compressed medical oxygen, or aerosol (r) Allergenio’ extra&s that are la-
products that depend upon the power of packaging and labeling to 00mPlY with tion of each lot of drug produot can be
a liquefied or compressed gas to expel the requirements of this seotlon. beled “NO. US. Standard of Poteno3;” readily determined to faoflitate its re-
the contents from the container) is re- Changes in paakaging and lab.eling re- are’exempt from the requirements of call if necessary.
quired to bear a statement that: quired by thisregulation may be made this section.
(i) Identifies all tamper-evident fea- before FDA approval, as provided under (g) New- drug’ produo.ts for investiga- Subpurt I-Laboratory Controls
ture(s) and any capsule sealing tech- §314.70(0) of ‘this .chapter. Manufa+ tional use are exempt from the. require-
nologies used to comply with para- turing .ohangea by whioh oapsules are ments of this seotion, provideh~ that 9211.160 General require&ents.
graph (b) of this section; to be sealed require prior FDA approval they : meet appropriate standards or
(ii) 1s prominently placed on the under @14.70(b)of this chapter. : speoifloations as demonstrated by sta- (a) The establishment of any speci-
bility studies during their use in clin- fioations, standards, sampling plans,
package; and (f) Poiso?zPreueittfon Packagfng Act o/ test procedures, or other laboratory
’ (iii) Is so placed that it will be unaf- 1970. This seotion does not affeot any ical investigations, Where new drug
fected if the tamper-evident feature Of produots for investigational use are to ‘control mechanisms required by this
requirements for “special packaging” subpart, inoluding any change’ in such
the package is breached or miSSini%. as defined under $310.3(l) of ,&is ohap- he reoonatituted at. the’ time of dia-
(2) If the tamper-evident feature sho- pensing, their IabeJing shall bear expi- speoifloations, standards, sampling
ter and required under the Poison Pret plans, test procedures, or other labora-
sen to meet the requirements in para- vention Paokaging Act of 1970. ration information for the reoonsti-
graph (b) of this section US;;~~ identi- tuted drug produot. tory control mechanisms,. shill be
fying characteristic, char- (Approved by the Office of’Management.and Ch) Pending. oonsideration of a pro- drafted by the appropriate orgsniaa-
acteristic is required to be referred to Budget under OI&Eooatrol number 0910-0149) ‘posed exemption, published in the FED- tional unit and reviewed and approved
in the labeling statement. For exam- [54 FR 52&, Feb. 2, 1989, a~ an’endedat 63FR ERAL REGISTER of September ‘29, 1978, by the quality control unit. The re-
ple, the labeling statement on a bottle 59470,Nov.4,1998] the requirements in this section shall quirements in this subpart shall be fol-
with a shrink band could say “For Your not he enforced. .for human OTC drug lowed and shall be documented at the
protection, this bottle has an im- Q211.154 Drug product inspection. produots if their labeling doesnot bear time of Performance. Any deviation
printed seal around the neck.” dosage limitations and they’are stable from the written specifications. St-d-
(a) Paokaged and labeled products ards; sampling plans., test prodedures,
(d) Request for exemptions from pack- shall be examtned during finishing op- fat at least S years as supported by ap-
aging and Labeling requirements. A man- propriate stability data, * . or other laboratory control mecha-.
ufacturer or packer may request an ex- erations to provide assuranoe that oon- nisms shall be recorded and justified;
emptiou from the packaging and label- tainers and packages .in the lot have M3 FR 45077,Sept. 29, 1978,as amendedat 46 @) Laboratory controls shall include
ing requirements of this section. A re- the oorreot label. FR W12. NOV.17.,198l: 65 FR 4091, Jan. 20, the establishment of scientifically
quest for an exemption is required to (b) A representative sample of units 19951
sound and appropriate specifioatfons.
be submitted in the form of a Citi’iien shal1. be oolleoted at the completion of standards, sampling pIa&. and test
petition under $10.30 of this chapter finishing operations and shall be vis- . Stibparf H-Holding and probedures designed ,to assure that
and should be clearly identified on the ually examined for .oorreot labeling. Disfribuffon components, ‘drug product containers.
envelope as a “Request for Exemption (0) Results of these examinations olosures. In-processmaterials, labeling,
from the Tamper-Evident Packaging shall be reoorded in. the batoh produo- 02ii.142 Warehousing &rooeduree. and . drug products conform to appro-
Rule.” The petition is required to con- tion or control reoords. .: Written procedures desoribing the priate standards of identity, strength,
tain the following: warehousing of. drug products shall be quality,. and purity. Laboratory oon-
(1) The name of the drug product or, $211.137 Expiratidn dating. trols shall include:
established and followed. They shall in-
if the petition seeks an exemption for a (a) To assure that a drug product oluqe: ’ (1) Determination of oonformaritie to
drug class, the name of the drug class, meets .applicable standax@ of identity, (a) Quarantine of drug produots be- appropriate written specifications for
and a list of products within that class. strength, quality, and purity’ at’ the fore release ‘by the quality oontrol the aoceptance.of each lot within each
(2) The reasons that the drug prod- time of use, it ohall bear an expiration unit, shipment of components, drug product
uct’s compliance with the tamper-evi- date determined by appropriate Sta- containers, closures, and labeling used
dent packaging or labeling require- (b> Stirage of drug. &oducts under
bility testing described in. 5211.166. appropriate conditions of temperature, in the manufaoture, processing, paok-
ments of this section is unnecessary or (b) Expiration’dates shall be related ing, or holding of drug products; The
cannot be achieved. h.umidity, and light so that the iden-
to any storage oonditions.stated on the tity, strength, quality, and purity of specifications shall include a descrip
(3) A description of alternative Steps labeling, ,as determined by stability tion of the sampling and testing proce-
that are available, or that the peti- the drug Products are not affected;
studies described in $211.166. dures used. Samples shall be represent-
tioner has already taken, to reduce the 0211.160 Distribution procedures., ative and adequately identified. Such
likelihood that the product or drug (c) If the drug product is to be reoon-
stituted at the time of dispensing, it8 procedures shall also require appro-
class will be the subject of malicious Written procedures shall’ be .estab- priate retesting of any component,
adulteration. labeling shall bear expiration informa- lished, and followed, desoribing the dis-
tion for both the reoonstituted. and drug product container, or closure that
(4) Other information justifying an tribution of drug products. They shall is subject to deterioration.
. exemption. unre’oonstituted drug products. inolude: .
. (d) Expiration dates shall appear on (2) Determination of conforinance to
(e) OTC drug products subject to ap- (a) A procedure whereby. the. oldest written speoiffoations and a descrip
proved new drug applications. Holders of labeling in accordance with the re- approved stock of a drug produot is dis-
quirements of 5201.17of this chapter. tion of sampling and testing procedures
approved new drug applications for trfbuted f&st. Deviation &rim TheaTR- ffinr (nnmnanr --L--l-*- .“-- -*
’
.

2) CFRch, I (4-l-00 EdItIon) food and Drug Admlnlstration,HHS 0211,170
$211.165
(e) The aoouraoy, , sensitivity, ‘apeoi- appropriate expiration date deter- rillty and pyrogen testing.. The reten-
shall be representative and properly minea. tion time is as iollows:
identified. ficity, and reproduofbllfty of test
methods employed by the. firm shall be (o), For homeo$&o drug. proiiuots (1) For an active ingredient in a drug
(3) Determination of conformanoe to the requirements of this seotion are & produot other than those described in
written descriptions of sampling proce- established and dooumented. Suoh vali-
dation’ and dooumentation: may be ao- follows: 9 paragraphs (a) (2) and (S) of this seo-
dures and appropriate specifications aooordance with (1) There shalL be a writ&n assess- tion, the reserve sample shall be re-
for drug products. Such samples shall complished in
5211194(a)(2). ‘ment of stability based at least on test- tained for 1 year after the. exniration
be representative and properly identi- (f) Drug products failing to meet es- ing or examiiration’of the drug product date of. the last lot of the drug product
fied. tablished standards or specifications for oompatibility of the .ingreiiients, containingthe active ingredient.
(4) The calibration of instruments, and any other relevant quality control and based on marketing experience (2) For ‘an active ingredient in a ra-
apparatus, gauges, and recording de- criteria shall be rejected. Reprocessing with the drug product to indicate that dioactive drug product, except for non-
vices at suitable intervals in accord- may be.performed.-Prior to acceptance ‘ther’e is no degradation of the product radioaotive reagent kits, the reserve
ance with an established written pro- and use, reprocessed material must for the normal or expected period of sample shall be retained for:
gram containing specific directions, meet appropriate standards, speoiflca- use.. (I) Three months after the expiration
schedules, limits for accuracy and pre- tions, and any ,other relevant ‘oritieria. (2) Evaluation. of stab&Y shall be date of the last lot of the drug product
c&ion, and provisions for remedial ao- based...on the same ..oon&er-olosure containing the active ingredient if the
tioa in the event accuracy and/or preci- 0 zll.l& .Stabi.li& t&i&& 8Ystem in whioh the drug .product is pxpiration dating period of the drug
sion limits are not met. Instruments, (a) There shail he a written testing being marketed.’ .‘: product .is 30 days or less; or
apparatus, gauges, and recording de- program designed to assess the sta- (d) +llergenio extra& that are la-’ (ii) Six months after the expiration
vices not meeting established specifioa- billty~oharaoteristics of drug produots, ‘beled. “No U.S. Standard ..of Potency” date of the last lot of the drug product
tionsshall not be used. The results of suoh stability testing are exempt from the requirements of containing ‘the active ingredient if the
$211.165 Testing and release for dir- shall be used in, determining appro- this section. expiration .dating period of the drug
tribution. prlate storage oonditions and expira- i49’FR 46077,Sept. 29 1978;‘&‘&&ded at 46 produot is more than 30 days.
tion dates. The wrftten program shall FR 58412,Nov..R, (S) For an active ingredient in an
(a) For each batch of drug produot, I be followed and shall .Inoludei : :’ 198ij : .: .. OTC drug product that i.s exempt from
there shall be appropriate laboratory (1) Sample. size and test fntervals 3211.167 Sphial testing reqllhmeats. bearing an expiration date under
determination of satisfactory Conform- based on stafdstloal. criteria for each 9211.137,’the reserve sample shall’be re-
ance to final specifications for the drug attribute examined to assure valid it&l- ,‘(a) For eaoh ’ batch . of drug’ ‘prbduot tained for 3 years after distribution of
product, including the identity and mates of stability; purporting to .be sterile and/or’&rogen- the last lot of the drug product con-
strength of each active ingredient, (2) Storage conditions for samples re- free, there. shall be appropriate iabora- taining the active ingredient.
prior to release. Where sterility and/or tained for testing; ’ tars testfig to ddt+niine oonforinanoe (b),’ An appropriately identified re-
pyrogen testing are conducted on spe- (3) Reliable, meaningful, and specific to such requirements; The test proce- serve sample that is representative of
cific batches of shortllved radio- test methods: dures sharl be in writing and shaU be each lot or batch of drug produot shall
pharmaceuticals, such batches may be (4) Testfng of the drug product in the fol,lotied. - he retainedand stored under conditions
released prior to completion of ste- same container-olosure system as that @) For each batoh: of ophthalmic consistent with product labeling. The
rility and/or pyrogen testing, provided in which the drug produot is marketed; ointment, there shall be appropriate
such testing is completed as soon a8 (5) Testing of drug produots for re- testing to determfne oonformance to reserve sample shall be stored in the
possible. oonstitutlon at the time of ‘dispensing speolfi cations regarding. the’presence of tem in whioh the tiontainer-olosure
same immediate
drug product is
sys-
mar-
(b) There shall be appropriate labora- (as direoted in the labeling) !a8 well as foreign partioles and harsh’ or’ abrasive keted or in one that has essentially the
tory testing, as necessary, of each after they are reconstituted... substanoes. The test prooedures shall same characteristics. The reserve sam-
batch of drug product required to be (b) A-n adequate number of batches of be in writing and shall befollowed. ple consists of at least twice the quan-
free of objectionable microorganisms. each drug produot shail be .te.sted to de- (a) For each batch of co&rolled-re:
(c) Any sampling and testing plans termine .an appropriate expiration date lease dosage form, there shall be.appro- quired~neoessary
tity to perform all the re-
.tests, except those for sterility
shall be described in written proce- and a record of such data shall. be priate laboratory testing to determine and pyrogens. Except for those for drug
dures that shall include the method of maintained. Accelerated studies, com- conformance to the sP,eoiifioatlone for products described in paragraph (b)(2)
sampling and the number of units per bined with basic stability information the rate of release of each active ingre-
batch to be, tested; such written proce- on the components, drug products, and dient, The test procedures shdl of this section,
be in representative. sample ‘reserve samples from
lots or batches
dure shall be followed. container-,olosure system, may be used writing and shall.be followed. selected by acceptable statistical pro-
(d) Acceptance .criteria for the sam- to support tentative expiration dates Oil1.170 Resefve samples. cedures shall be examined visually at
pling and testing conducted by the provided full shelf life studies are not least once a year for evidence of dete-
quality control unit shall be adequate available and are being conduoted. .(a) An approptiately identified re- rioration unless visual examination
to assure that batches of drug products Where data from aooeIerated studies serve sample that is representative of would affeot the integrity of the re-
meet each appropriate specification are used to projeot a tentative explra- eaoh lot in each.shipment of each ac- serve sample. Any evidence of reserve
and appropriate statistical quality con- tion date that is ‘beyond a date sup- tive ingredient shall be retained. The sample deterioration shall be Ives-
trol criteria as a condition for their ap- ported by actual shelf life studies, reserve sample coiisists ‘of at least tlgated in accordance with $211.192.
proval and release. The statistical there ,must be stability studies cop- twice the quantity :necessaxy- for all The results of the examination shall be
quality control criteria shall include duoted, inoludfng drug product testing tests required to determine whether reoorded and maintained with other
appropriate acceptance levels and/or at appropriate intervals, until the .ten- the active ingredient meets its estab- stability data on the drun aradwt. IL-
appropriate rejection levels. tative expiration date is verified or the lished specifioatlonn. .w,w.+ i- -I-’
: 21 CFRCh. I (4=+00idltlon) Pooh and Drug Admihlstratio~,HHS §21i;186
~211.173
gases need not be retained. The reten- Register, 800 North Uapitol Street, eaoh drug produot :to determine the 0211.1&i Component,
NW;, suite 700,Washington, DC120408. need for changes in drug produot speoi- container, doiwre, tit!an lz%Tr;
tion time is as follows: records..
(1) For a drug product other than fioations or mahufaoturfng or. control.
[43FR 45077,Eiept.29, 1978,&mended at 47 procedures. Written procedures shall be
those described in paragraphs (b) (2) FR 9396,,Mar.6, 1981;SOFR 8998, Mar. 6, 1985: These records shall include the. fol-
and (3) of this section, the reserve sam- 55 FR 11677,
Mar. 29,lSSO] established and followed for. such eval- lowing:
ple shall be retained for 1 year after uations and shall include: provisions (a) The identity and quantity of each
the expiration date of the drug prod- Subpart J-&cords and RBports ior: I . shipment of each lot of components,
uct. ‘(1) A review ef a representative num- drug product containers, closures, and
(2) For a radioactive drug product, 92ll.180 Gtmerai requirements. ber of batches, whether approved or rel labeling: the name of the supplier; the
exceDt for nonradioactive reagent kits, (a) Any production, control, or dis- jetted, and, where applioable. Teoords. supplier’s’ lot number(s) if known; the
the reserve sample shall be retained tribution reoord Fiat is required to be associated with the batch. receiving code as specified in 9211.80;
for: maintained in compliance with this (2) A review of oomp&ints, recalls, and the date of receipt. The name and
(i) Three months after the expiration part and is speoifioally assooiated with . returned or salvaged drug. products, location of the prime manufacturer, if
date of the drug product if the expira- a batch ‘of a drug produot shall be re- and investigations oonducted . under different from the supplier, shall be
tion dating period of the drug product tained for. at leas%i year after the expi- §211.192for eaoh drug produot. I .; listed if known.
is 30 days or less; or ration date of the batch or, in the case @) The results of any .test
(ii) Six months after the expiration of certain OTU drug products laoking
(0 Prooedures shall be established to . . .or exam-
assure that the responsible offloials of ination performed (Incluamg tnose per-
date of the drug product if the expira- expiration dating because they meet the firm, if they are not personally in- formed as required by 5211.82(a),
tion dating period of the drug product the oriteria for exemption under volved in or immediately ‘aware of such §211.84(d>,or 5211.122(a)) and, the oon-
is more than 30 days. $211.137, 3 years ‘after distribution of
aotions, axe notified in. writing of any .olusions derived therefrom.
(3) For an OTC drug product that is the batoh. (0) An individual inventory record of
exempt for bearing an expiration date (b) ReoQrds shall be .maintatned for :investigationa ooriduoted : under
O~211.198, 211.204,or $1.208’of these reg- each. component, drug product con-
under 6211.137,the reserve sample must all components, drug produot con- tainer, and closure and, for each com-
be retained for 3 years after the lot or tainers, olosures, and- labeling for at ulations, any reoalla, reports of
inspeotional observations issued by the ponent, a reconciliation of the use of
batch of drug product is distributed. least 1 year after the expiration date eaoh lot of such component. The inven-
or, in the ease of certain OTU drug Food and Drug Administration, or any tory record shall contain s.uffioient in-
[48 FR 13025.Mar. 29, 1983.as amendedat M) produots laoking expiration dating be- regulatory a&ions relating to goqd
FR 4091.Jan. 20. 19951
cause they meet the criteria for exemp- formation to .allow determination of
m+mfaoturing praot’iges brought by ans batoh or lot of drug product assocl-
$211.173 Laboratory animals. tion under l2&1.137, 3 years after dis- the Food and Drug Admimstration, ated with the use of eaoh component,
tribution of the last lot of drug Product drug product container, and closure.
Animals used in testing components, incorporating the component or using [43 FR’45077,Sept. 29, 1978,as amendedat 60
in-process materials, or drug products the container, closure, orlabeling. FR.4091,Jan. 99,1995] (d) Documentation of the examina-
for compliance. with established speci- (c) Al1 records required under this tion and review of labels and labeling
fications shall be maintained and oon- part, or Qopies of suoh reoords, shall be Px1I.l.. Equipment clean& and use. for conformity with established speci-
trolled in a manner that assures their readily available for authorized inspeo- . fications in accord with f§211.122(c)and
suitability for their intended use. They tion duririg the retention period at the A written record of major equipment 211.130(c);
shall. be identified, and adequate establishment where ,the activities de- oleaning, mainteqanoe (exoept .routine (e) The disposition of rejected compo-
records shall be maintained showing scribed-in such records ooourred, These maintenance such’ as lubrfoation .and nents, drug product containers, olo-
the history of their use. records or copies thereof ‘shall be sub- adjustments); and use shall be included sure, and labeling.
$211.176 PeniciUin contamination, ject to photooopying or other means of in individual equipment logs that show OSll&ii6~~~
reproduction as part of such inspeo- the date; time, ,produ+;‘&d lot number production and con-
‘If a reasonable possibility exists that tion. Reoords that oan be immediately of each batch processed. Jf ‘equipment
a non-penicillin drug product has been retrieved from another location by is dedicated to manufaoture .of one (a) To assure’uniformity from batch
exposed to cross-contamination with computer or other ele&ronic means product, then individual equipment to batch, master production and con-
penicillin, the non-penicillin drug prod- shall be oonsidered as meeting the re- logs’ are not required, ‘provided that trol records for each drug product, in-
uct shall be tested for the presence of quirements of this paragraph, cluding each batch size thereof, shall
penicillin. Such drug product shall not (d) Records reQuired under this part lots’ or batches of suoh product follow
be prepared, dated, and signed (full sig-
in numerical order and are’ manufac- nature;
be marketed if detectable levels are may be retained either as original handwritten) by one person and
found when tested according to proce- records or as true oopies such as photo- tured in numerical sequende. In cases independently checked, dated, and
dures suecified in ‘Procedures for De- copies, microfilm, microfiche, or other where dedicated equipment . is em- signed by .a second person. The prepara-
tecting-and Measuring Penicillin Con- accurate reproductions of the original ployed, the records of oieaning, main- tion of master productfon and control
tamination in Drugs,’ which is incor- records. Where reduotion techniques, tenance, and use shall be part of the reoords shall be described in a written
porated by reference. Copies are avail- such as miorofflmfng, are used, suit- batoh record. The persons performing procedure and such written procedure
able from the Division of Research ‘and able reader and photocopying equip- and double-cheokfng the cleaning and shall be followed.
Testing (HFD-470), Center for Drug ment shall be readily available, maintenance shall date and sign or ini- 01) Master production and control
Evaluation and Research, Food and (e) Written records required by this tial the logindicating that the work records shall include:
Drug Administration, 200 C St. SW., part shall be maintained so that data was performed. Entries in thd log shall (1) The name and strength of the
Washington, DC 20204,or available for therein oan be used for evaluating, at be.in ahronologfoal order. product and s description of the dosage
inspection at the Office of the Federal least annually, the quality standards of form:
/ , ..’

§zwa *:21 CFR'Ch;l(+OO Ec?tldn) .§211.198
(2) Identity of individual major nedessary ’ to assure oomPliance ‘with (7) The initials or signature of the
(2) The name and weight or measure established speoifications,~~,&d stand- person who performs eaoh test and the
of each active ingredient per dosage efluipment and lines used;
(3) Speoific identification ‘of each ards, including exam&& ons’ and as- date(s) the tests were performed.
unit or per unit of weight or measure saye, as follows: ’ . :~- - (8) The initials or signature of a ae’c-
‘of the drug produot, &nd a statement of batoh pi component or in-process mate-
rial used; ‘, (1) A desoription ‘of the ,sample re- ond person showing that the original
the total weight or measure of any doe- oeived for testing with identification of records have been reviewed far accu-
age unit: (4) Weights and measures ,of obmPo-
(3) A complete list of components nents used in the oourse of Prooesaing; soyrbe (that is, location from where raa$, completeness, and oompliance
designated by names or codes suffi- (5) In-prooess and laboratory oontrol sample was obtained), quantity, lot with es$ablished standards.
results; ‘number or other distinctive code, date @) Gomplete records shall be main-
cientlv soecific to indicate any speolal
quality characteristic: (6) Inspection of the packaging and sample was taken, and date sample was tained of any modification of an estab-
(4) An accurate statement of the labeling area before and after use; reaeived for testing. lished method employed in testing.
weight or measure of each component, (7) A statement of. the actual yield (2). A statement of each method used Such reoords shall include the reason
using the same weight system (metric, and a statement of the percentage of in the testing of the sample. The,state- for the modification and data to verify
avoirdupois, or apothecary) for each theoretiaal yield at appropriate. phases ment shall indicate the location of that ‘the modification Produced results
component. Reasonable variations m&y of proaessing; data that establish that the methods that are at least as scourate and reli-
be permitted, however, in the amount (8) Complete labeling oontrol records, used in the testing of the sample meet the able for the material being tested 8s
0;’ components necessary for the prepa- including speoimens or copies of all la- proper standards of aocuraoy ,e,.ndreli-, established method.
.. . beling use& (0) ‘Complete records shall be main-
ration in the dosage form, provlaea ability as applied to the product tested, tained’of any testing and standardiza-
thev are justified in the master produc- (9) Desoription of drug product oon- (If the .method employed is in the cur- tion of laboratory reference standards,
tici and control records: tainers and closures; rent revision of. the ‘United States reagents, cind standard solutions,
(5) A statement concerning any cal- (10) Any sampling Performed;
(11) Identification of the’ persons Per- PharmaaoPeia, National Formulary, (d) ComPlete records shall be main-
culated excess of component; Association ‘of Offioial tialytical
(6) A statement of theoretical weight fo&g snd direotly .suPervising or tained of-the periodfo oalibration of
checking each significant step in the Chemists,
->. Book _. of . Methods,’ or in laboratory instruments, apparatus,
or measure at appropriate phases of I otn.er recognized standard references, gauges, tlnd recording devices required
processing: operation;
(U) Any Investigation made accord- or is detailed in an ‘&Proved. new drug by 5211.166(b)(4).
(7) A statement of theoretical yield, applicatfon and the referenced method
inoiud?.ng the maximum and minimum ing to 5311.192. (e) Complete records shall be main-
cercentaaes of theoretical yield beyond (13) Results of examinations made in is not modified, a statement bdioatifig tained of all stability testing- per-
‘w~hich investigation according to accordance with $211.154. the method and reference will suffioe). formed in accordance with 521x.166,
$211.192is required; .The suitability of all testing methods
Q211.192 Production record review. used shall be verified under actual con- FR 143FR 450’71,Sept. 29. 1978,as amended at 55
(8) A description of the drug product 11577,Mar. 29,1990]
containers, closures, and packaging All drug product’production and con- ditions ,of use:.
materials, including a specimen or trol records, including those for Pack- (3) A statement of the .weight or Q211.196 JXsMbution records.
copy of each labe! and all other label- aging and labeling, shall be reviewed measure of sample used for es& test, Distribution records shall contain
ing signed and dated by the person or and approved by the Quality control where apProPriat& the .name and strength of the product
persons responsible for approval of unit to determine aompliarioe with all ‘(4) A complete record of all data se- and description of the dosage form,
such labeling: established, aPproved written prooe- cured in the course of eaoh’teet, inalud- name and address of the consignee,
(9) Complete manufacturing and con- dures before a batoh is released or dis- lag all grrtghs, charts, and speotra from date and quantity shipped, and lot or
trol instructions, sampling and testing tributed. Any urnexPlained discrepanay laboratory instrumentation, Properly aontrol number of the drug product.
procedures, specifications, special no- (including a Peroentage of theoretical identified to show the speaifio oompo- For. compressed medical gas Products
tations, and precautions to be followed, yield exoeeding the r&ximam or min- nent, drug Product container, closure,, distribution records are not required td
imum peroentitges established in mas- in-RrOceSS material, or $rug produot,
3 211r.;t18r%atch production and control ter production and control records) or Contain lot or oontrol numbers,
. the failure of a batch or any of its aom: and. lot tested,
(5) .A record of all oa&ations (ADPrOVed
per- Budget under by the. Office of Management snd
Batch production and control records ponents to meet any of its specifica- coqtrol number 091&o139)
tions shall be thoroughly investigated, formed in oonneotion v;ith tlie&tst; in-
shall be prepared for each batch of drug cluding units’ of measuri, co&ersion [49 FR 9865,Mar. is19843
product produced and shall include whether or not the batoh has already
been distributed. The investigation factors, and equivalency factors. 4211.198 Complaint files.
complete information relating to the
production and control of each batch. shall extend to other batches of the (6) A statement of .the results of tests.
and ‘how the results compare with es- (a) Written procedures describing the
These records shall include: same drug product. and. other drug handling of all written and oral com-
(a) An accurate reproduction of the products that ‘may have been assoob tablished standards of identity,
approhriate master production or con- ated with the specific failure or dis- Strength, quality, and Purity for the Plaint5 regarding a drug product shall
component, drug Product container, be estsblished and followed, Such pro-
trol record, checked for accuracy, crepancy. A written record of the in- cedures shall include provisions for re-
dated, and signed; vestigation shall be made and shall in- closure, in-Process, material, or drug
product tested. view by the quality control unit, of any
(b) Documentation that each signifi- clude the oonclusions and followup. L COmPhint involving the possible fail-
cant step in the manufacture, proc- ure of a drug product to meet any of its
essing, packing, or holding of the batch $211.194” Laboratory recoiih ‘Copf8s may be obtained nom: Association SPeCiilOatiO~ and, for such drug prod-
was accomplished, including: (a) Laboratory reoords shall include Of Offioial Analytical, Ubemfste,2QQQ Wilson ucts, a de~minatinn n- +- cL - -
(1) Dates: complete data derived from all tests Blvd., Suite-400,Arlfngton. VA CJWM’ -fi-
21 CFRCh, I (4-1~00Edition) Food and Drug AdmInIstratIon,HHS §216,24
g211.204
that the drug produots meet all ‘appli- BeriOxavrafen: All drug products c&ta.ining
$211.192.Such procedures shall incl.ude Subpart K-Returned’ and cable standarda. of identity, strength, benoxaprolen.
provisions for review to determine Salvaged Drug Products .quality, and purity and. (b) evfdenoe Bfth~onol: All drug products containing
whether the complaint represents a se- from inspection of the premises that bithionol.
rious and unexpected adverse drug ex- S211@4' Returz.aed drwproducte. Bromfenac sodtum: All drug products con-
the drug products and their assooiated taining bromfenao sodium.
perience which is required to be re- Returned drug products shall be iden- paokaging were not subjected’ to im- Butumben: All parenters drug producti con-
ported to the Food and Drug Adminis- tified as suoh and held. If the oondi- proper storage aonditiona aa a result of Wining butanibea.
tration in accordance with $310.305of tions under which returned drug prod- the disaster or aocident, Organoleptio Camvhoiated oil: All drug products con-
this chapter. ucts have been held, stored,. or shipped examinations shall be acceptable only taining camphoratedoil.
(b) A written record of each oom- before or during their return, or if the as supplemental evidence that the drug Carbetapkrtane citrate: All oral gel drug prod-
plaint shall be maintained in a file des- condition of the drug product, its con- products meet appropriate standards. of uots containing carbetapentanecitrate.
tainer, carton, or labeling, as a result identity, strength, quality, an@purity; Casetn, fodfnuted: All drug Produots con-
ignated for drug product complaints+ taining iodinsted oasein.
The file regarding such drug product of storage or shipping, casts doubt on Records including name, lot number, Chlorhezidtne gluconate: All tinctures of
complaints shall be maintained at the the safety, identity, strength, quality and disposition shall be malntained for ohlorhexidiae gluconate formulated for use
establishment where the drug product or purity bf the drug product, the re- drug produote subjeot to this section. as a patient preoperative skin preparation.
involved was manufactured, processed, turned drug uroduot aball be destroyed Chlormadinone acetute: All drug produota con-
or packed, or such file may be main- unless examination, testing, or other PART2 16-PHARMACY taining chlormadinone acetate.
investigations prove the drug product Chloroform: All drug produots containing
tained at another facility if the written meets apprcpriate’standards of safety, COMPOUNDING chloroform.
records in such files are readily avail- identity, strength, quality, oripurity. A Cobalt: All drug products oontafning cobalt
able for inspection at that other facfl- drug prcduot may be reprocessed Rro- Subpart A-Gener~ ProvIsIons[ReservedI salta (eXOePt radioactive forma of cobalt
ity. Written records involving a drug vided the subsequent ‘,.drug; product and it8 da.lts.and cobalamin and its deriva-
product shall be maintained until at Subpart B-Compounded Drug Products tives).
meets appropriate standards, ‘speoifioa- DWeW~ramine hydrochlorkie: All drug prod-
least 1 year after the expiration date of tions, and oharaoteristics. Reoords of Sec.
the drug product, or 1 year after the uots oontafning dexfenfluramine hydro-
returned drug produots shall be main- 216.22 Deserved] ’ chloride.
date that the complaint was received, tained and shall include the name -and 96.24 Drug Products withdrawn dr removed Diamthazole dihydrochlor@e: Ml drug prod-
whichever is longer. In the case of cer- label potenoy of the drug produot dos- from the market for reasonsof safety or ucte oontaiLung d.iamtbasole
tain OTC drug products lacking expira- age form. lot number (or oontrol num- effeotiveness. dibydroohloride.
tion dating because they meet the ori- b& or ba&h number), reason for the re- AU~HORITX21'U.S.C. 25i, 252,35Sa,555,and Dibromsalan: All drug products containing
teria for exemotion under 5211.137,such turn, quantity returned, date of dis- 571. dibromsalan.
written records shall be maintained for Dteth#sttlbestrol: All oral and parenteel drug
uosition, and ultimate disposition of MJRUE: 64 FR 10844, Mar. 8, 1999, unless products containing 25 milligrams or more
3 years after distribution of the drug the returned drug prq~uct. If the rea- otberwis~ noted. ..Ofdfethylstilbestrol per unit dose.
product. son for a drug product being returned . * Dih~drostrevtomwin sulfate: All w products
(1) The written record shall include implicates associated. batches, ah ap- Subpart A-Gerwral Provisions containing dihydrostreptomycin sulfate.
the following information, where propriate investigation shall be con- preserved] Wmme: All drug products containing
known: the name and strength of the ducted in accordance with the require: dipyrone.
drug product, lot number, name of ments of 3211.192. Procedures for the Encaintde hydrochloride: All drug produces
complainant, nature of complaint, and holding, testing, and reprocessing of re- ‘Subpatf B-Compoundqd Drug containing encainide hydroohloride.
Products Fenj7uramtne hydrochloride: All drug prodiots
reply to complainant. turned drug products shall be. in writ- containing feniluramine hydrochloride.
(2) Where an investigation under ing and shall be followed. : ~oseWfnw: All drug produota containing
O216.23 lReservedl floeeauinan.
$211.192 is conducted, the written 0 211.208 ,Drug product salvaging.
record shall include the findings of the 021&!24 ‘Drug produote withdrawn or Gelatin: All intravenous drug products con-
Drug products that have been sub- removed from the market for rea- GlyCerol, taining gelatin.
investigation and followup. The record fodfnated: All drug products con-
or copy of the record of the investiga- jected ,to improper storage oonditions so* of safety or effiwtiveness. taining iodinated glycerol.
tion shall be maintained at the estab- including extremes in temperature, hu- The following drug produots were .GoWdotrovfn, chorfonfc: All drug products
lishment where the investigation oc- midity, smoke; fumes, pressure, age,, or withdrawn or removed from the mar- containing chorionic gonadotropins of ani-
curred in accordance with ~211.180(0). radiation due to natural disasters, ket because suoh drug producta or com- mal origfn.
(3) Where an investigation under fires, accidents, dr equipment failures ponents of suoh drug produots were Mew&e: All drug products containing
shall not be salvaged and returned to found to be unsafe or not effective; The mewine hydrochloride or mepszine ace-
tj211.192is not c’onducted, the written the marketplaoe. Whenever there is a tate.
record shall include the reason that an fOllOwing drug products may not be Metabromsalan: All drug products containing
question whether drug products have compounded under the exemptions pro-
investigation was found not to be nec- been subjected- to such conditions, sal- metabromsalan.
essary and the name of the responsible vided by section 603A(a) bf the Federal Methamvhetamfne hydrochloride: All paren-
vaging operations may be conduoted Food, Drug, and Cosmetic Aot: ‘teral drug Products containing meth-
person making such a determination. only if there is (a) evidence from lab-
Adenosfne vhosvhate: All drug produota con- amphetamine hydrochloride.
[43FR 45077,Sept. 29.1978,as amendedat 51 oratory tests and assays (including.ani- Methmdlene: All drug products containing
<FR 24479, July 3. 19861 ma1 feeding studies where applicable) taining adenosiaephosphate. a methapyrilene.
. Adrenal carter: All drug prod&a containing Methovholfne: All drug produots containing
adrenal.cortex. methopholine.
kzarfbfne.’ All drug products containing Mfbefradtl dfh~drochloride: All drug Products
azaribine. Mnmninw mihm%AO ALA-- -a * *-
ublic health e
medical profc
continuing to warn
the dangers of ultr:
radiation from the
beds, and sun lamp
ultraviolet radiatio:
violet A (UVA) ant
(UVB), UVB has 1~
ciated with sunburr.
has been recognize
penetrating radiatic

Although it’s been 1
some time that too :
radiation can be har
information may nc
warnings even mar-
Somescientists ha\
recently that there I
association betwee:
tion and malignant
most serious type 0

C 1996 Amertcanhdemy of Dermatology
Addmu cdpics available from:
..a*.,
l ‘-. ~rricar A&emy 01 Dermatology
P 0 601 401-l
:‘;“’
*., ,.’ QWvrnburg. IL 60168~4014
ublic health experts and What are the dangers,of tanning?
UV radiation from the sun, tanning beds, or from sun
medical professionals are lamps may cause skin cancer. While skin cancer has
continuing to warn people about been associatedwith sunburn, moderate tanning may
also produce the sameeffect; UV radiation can also
the dangers.of ultraviolet (UV) have a damaging effect on &heimmune system and
radiation from the sun, tanning cause premature aging of the skin, giving it a
beds; and sun-lamps. Two types of wrinkled, leathery appearance.

ultraviolet radiation are Ultra- But isn’t getting some sun good
violet A (UVA) and Ultraviolet B for your health?
People sometimes associate a suntan with good health
(UVB). UVB has long been asso- and vitality. In fact, just a small amount of sunlight is
ciated with sunburn while UVA needed for the body to manufacture vitamin D. It
has been recognized as a deeper doesn’t take much sunlight to make all the vitamin D
you can use - certainly far less than it takes to get a
penetrating radiation. suntan!

Are people actually being
Although it’s been known’for ’ harme.d by sunlight?
some time that too much UV Yes. The number of skin cancer caseshas been rising
radiation can be harmful, new over the years, and experts say that this is due to
increasing exposure to UV radiation from the sun,
information may now make these tanning beds, and sun
warnings even more important, lamps,-More than 1
million new skin cancer
Some scientists have suggested casesare likely to be
recently that there may be an diagnosed in the U.S.
association between UVA radia- this year.

tion and malignant melanoma, the
most serious type of skin cancer.

1 ‘. 2
But aren’t the types of skin cancer Who is at greatest risk in the sun? You can get a fact sheet on the hazards of indoor
caused by the sun, tanning beds, and People with skin types I and II are at greatest risk. tanning from FDA’s Facts on Demand system by
sun lamps easily curable? calling l-800-899-0381; the information will ‘be
Not necessarily. Malignant melanoma, now with a ” Which &in type aie you? faxed to you on the same day (select 2 and then
suspectedlink to UVA exposure, is often fatal, if not Division of Device User Programs and Systems
detectedearly. The number of casesof melanoma is Analysis or DDUPSA). You can also go to the FDA
rising in the,U.S., with an estimated 38,300 casesand Home Page on the World Wide Web at http://
7,3QOdeathsanticipated this year. .www.fda.gov. At this point, click on the Medical
Devices and Radiological Health icon, click on
Why doesn’t the skin of young Program Areas and chqose Radiation Injuries.
people show these harmful effects?
Skin aging and cancer are delayed effects that don’t Information on skin cancer is available on the
usually show up for many years after the exposure. American Academy of Dermatology (AAD) Home
Unfortunately, since the damageis not immediately Burns minimally; always tans well to Page,on the World Wide Web at http://www.aad.org.
visible, young people are
often unaware of the Whaf do medical professidnals .
dangers of tanning, say about tanning?
Physicians and scientists The American Medical Association (AMA)‘and
are especially concerned Never burns; dee the AAD have warned people for many years : y
that casesof skin cancer about the dangers of tanning. In fact, AMA and
will continue to increase AAD have urged action that would ban the sale
as people who are now in and use of tanning equipment for non-medical
their teens and twenties Since most’ sun lamps and tanning purposes. Doctors and public health officials
reach middle age. beds emit UVA radiation, doesn’t have recommended the following steps to
that make them safer than natural minimize the sun’s damageto the skin and eyes:
But why is it that some people can sunlight?
tan for many years and still not No. It’s true that most sun lamps emit mainly UVA l Plan our outdoor activities to
show damage? radiation, and.that these so-called “tanning rays” are ’ avoiB the sun’s strofigest rays.
Peoplewho chooseto tan are greatly less likely to cause a sunburn than UVB radiation As a general rule, avoid the sun between IO am. l

increasing their risk of developing skin from sunlight. But, contrary to the claims of some and 4 p.m.
cancer. This is especially true if tanning Atanning parlors, that doesn’t make them safe.
occurs over a period of years, because UVA rays have a suspected link to malignant l Wear protective covering
damageto the skin accumulates.Unlike melanoma, and, like UVB rays, they also may be such as broad-brimmed hats, long
skin cancer, premature aging of the skin linked to immune system damage. pants and long-sleeved shirts to
will occur in everyone who is repeatedly reduce exposure.
exposedto the sun over a long time, What’s the government’s position
although the damagemay be less apparent on using sun la@p products found l Wear sunglassesthat’providc
and take longer to show up in p’eoplewith .in tanning parlors and in hom’es? 100% UV ray protection.
darker skin. The Food and Drug Administration (FDA) and
the Centers for Disease Control and Prevention
(CDC) encourage people to avoid use of tanning beds
and sun lamps.
Who is at greatest risk in the sun? You can get a fact sheet on the hazards of indoor . Always wear a broad-spectrum
People with skin types I and II are at greatest risk. tanning from FDA’s Facts on Demand system by SUnSCrtXXl with Sun Protection Factor (SPF) I5
calling I-800-899-0381; the information will be ,, or more, which will block both UVA and UVB
Which skin type are you? faxed to you on the same day (select 2 and’ then when outdoors and reapply it according to ,
Diiision of Device User Programs and,Systems manufacturer’s directions..
Skin Sunburn and Tanning History Analysis or DDUPSA). You can.also go to the FDA
Type According to Skin Type Home Page on the World Wide Web at http://
www.fda.gov. At this point, click on the Medical . For more information
I Always burns; never tans; sensitivi
Devices and Radiological He$th icon, click On on the levels of
(“Celtic”)
Program Areas and chotise Radiation Injuries. ultraviolet radiation
II Burns easily; tans minimally reaching your area at
III Burns moderately; tans gradually to light Information on skin cancer is available on the noon, you can get the
brown (Average Caucasian) American Academy df Dermatology (AAD) Home Ultraviolet Index
IV Burns minimally; always tans well to Page on the World Wide Web at http://www.aad.org. (UVI) from local
moderately brown (Olive Skin) newspapers,radio or
What .do medical profession’z4ls TV in many cities.
V Rarely burns; tans proftisely to dark say about tanning? The UVI is a number from O-IO. The higher. the
(Brown Skin) The American Medical Association (AMA) and ” number, the more intense the exposure. Call the EPA
VI Never burns; deeply pigmented, not the AAD have warned people for many years . Hotlinefor more information on the UVI at 1-800-
sensitive (Black Skin) ‘about the dangers of,tarining. In fact, AMA and 296-1996.
AAD have urged action that would ban the sale
and use of tanning equipment for non-medical If you believe that some damage
Since most sun lamps and tanning pdrposes. Doctors and public health officials has already been done:
beds emit UVA radiation, doesn’t have recommended the following steps to . . Seek immediate medical attention if you
that make them safer than natural, minimiie the sun’s damageto the.skin and eyes: receive skin or eye damage from the sun
sunlight? or if you experience an allergic reaction to
\:o. It’s true that most sun lamps emit mainly UVA * Plan Fouroutdoor activities ‘to the.sun.
xdiation, and that theseso-called “tanning rays” are avoid the sun’s strongestrays. i See your dermatologist or personal
CBSlikely to causea sunburn than UVB radiation As a general rule, avoid the sun between 10 a.m.
:‘romstmlight. But, contrary to the claims of some and 4 p.m. physician if you develop an unusual mole,
tanning parlors, that doesn’t make them safe. a scaly patch or a sore that doesn’t heal.
WA rays have a suspectedlink to malignant l Wear protective covering
melanoma,and, like UVB rays, they also may be such as broad-brimmed hats, long.
pants and long-sleeved shirts to
reduce exposure.

on using sun lamp products found l Wear SUnglaSSeS that provide
in tanning parlors and in homes? 100% UV ray protection.

a. This Part provides for [the registration of tanning facilities using ultraviolet lamps, and] regulation
of the maintenance and operation of tanning facilities.

b. In addition to the requirements of this Part, al! fGl.ities are subject to the applicable provisionsof
other Parts ofthese regultitions.

c. Nothing in this Parr shall be inter&eted as fimiting the intentional exposure of patients to
ultravioiet tidiation for the purpose of treatment or use oomtnensurate with the .licensed
practitioner’s use of a healing art. . . . ?

Sec. BB.2 - Definitions. The following terms are defined for purposes of this Part.

“Act” means [cite State Radiation Control Act].

“Agency” means [cite appropriate State agency].

“Consumer” means any member of the public who is provided access to a tanning facility in exchange’for
a fee or other compensation’ or any individual who, in exchange for a fee or other cpmpen+io< is
afforded use of a tanning facility as a condition or benefit of membership or access.
“Kealing arts” means [cite appropriate. State definition].

“Individual” means any human being.

“Inspection” means an oflicial ek&iation or obServation including but not limited to test!s;sux$$, and
monitoring to.determine’compli&e with rules; regulations, orders, requirements a& conditions of the
AgepY. .
.
.:
: “License” means a license issued by the Agency in accordance with regulations issued by .the Agency-
~.
“Licensee” means any person who is licensed by the agency in accord&xx with these’regulations and the.’
Act.

“Operator“ means an individual designated by the registrant to control operation of the tanning facility
and to instruct and assist the consumer in the proper operation of the tanning equipment.

“Person” means any individual, corporation, partnership, firm, association, trust, estate, public or private
institution, group, agency, political subdivision of this State, any other State.or political

BBI
SSRCR V01umle N - Oclober 1996 %.x. BB.2 - BB.4

subdivision or agency thereof, and any le@ successor, representative, agent, or.agency of the foregoing.

“Radiation” means ultraviolet radiation.

“Radiation machine” means any device capable of producing radiation.

“Registrant” means any person who obtains a registration, license, permit or other entitlement from the
Agency, and who is obligated to obtain such registration, license, permit or other entitlement Corn the
Agency pursuant to these regulations and theAct.

a. Each’person having a tanning facility Shall apply for registration of such facility with the Agency,
within [30] days following the effective date of these regulations or thereafter prior to the .. :,
operation of a tanning facility. Application for registration &all.be completed on forms
satisfactory to the Agency and shall’contain,all the information required by the form and the
accompanying instructions.

BB2
Scc.BB.4 -BB.7 SSRCR I/o1:4meiI - October 1996

b. The Agency shall require at least the following information on the Application for Registration of
Tanning Facilities form:

i. Name, address and telephone number of the following:

(1) The tanning facility;
(2) The owner(s) of the tanning facility;

ii. The manufkcturer, model number, and type of each ultraviolet lamp or tanning equipment
located within the facility;
.I.
111. The’geographic areas within the State to be covered, if the fkility is mobile;

V. A signed and dated certification that the applicant has read and understands the
requirements of&se regulations; ‘. .’ -. . . ’ ,

vi. A copy of operating and safety procedures unique to facility operation. .

C. Each applicant shall provide such additional information as the Agency may reasonably require.
.
Sec. BBS - Issuance of Certificate of Retistration.

a- Upon determination that an applicant meets the requirements ofBB.4, the Agency shall issue a
certificate of registration

b. The Agency may incorporate in the certificate of registration at the time of issuance or thereafter.
by appropriate rule, regulation or order, such additionzil requirements a.ird conditions with respect
to the registrant’s receipt, posses&ox+ use,and transfer of tanning fac.Xties as it deems appropriate
or necessary.

Sec. BB.6 - Expiration of Certificate of Registration. Except as provided’in BB.7b., each certificate of
registration shall expire at the end of the specified day in the month and year statedtherein.’

Sec. BB.7 - Renewal of Certificate of Repistration.

a. Apphcation for renewal of registration shall be filed in accordance with BB.4.

b. In any case in which a registrant not less than 30 days prior to the expiration of his existing
certificate of registration has filed an application in proper form for,renewal, such existing

BB3
SSRCR Volutrle II - October 1996 See. BB.7 - BB. 1 I

certificate-of registration shall not expire until the application status has been finally determined by
the Agency.

Sec. BB.8 - Report of Chaqes. The registrant shall, notify the Agency in writing before makirtg any
change which would render the information reported pursuant to BB.4b.i., ii., iii. and vi., contained in the
application for registration or the certificate of registration, no longer accurate. This requirement shall
not apply for changes involving replacement of designated original equipment lamp types with lamps
which have been certified with the Food and Drug Administration as “equivalent” lamps under the Food
and Drug Administration regulations and policies applicable at the time of replacement of the lamps. The
facility owner, shall maintain manufacturer’s literature demonstrating the equivalency of any replacement
lamps.
.
S&. BB.9 - Transfer of Certificate ofRetistration. No certificatk’ofregistration shall be transferable
from one person to another or fi-om one tanning f&%ty to another. -

Sec. BB. 10 - - Apt&-oval Not Imulied. No’person,‘in any advertisemen~~shall refer to the fact that he or
h’ls f+ility is registered viith the &ency pursuant to the provisionsofBI3.4, and no person shall state or
imply that any activity under such registration has b.een approved*by the Agency. .
... .. . .
Sec. BB.11 - Denial. Susnension. or Revocation of Certificate of Registration.

a. The Agency may, for good cause shown, deny, suspend or revoke a certificate of~registration
sought or issued pursuant to these regulations for any of thefollowing reasons: . .
-
1. .Failure of :repo$,..pl&s or spezifica~ons to show that the .tanning facility will be’:
construeted,~ opera&l .or malntahted in accordance with the requirements of thtie
regulations;

iv. Operation of the tanning facilityln .i way that causes or &&es a n&an@ 6r hazard to the
public he&h orsafety;.

V. Violation of any rules, regulations, standards, or requirements adopted by the Agency;

vi. Violation of any condition upon which the certificate of registration wasissued;
vii. Failure to allow duly authorized age& of the Agency to conduct inspections at reasonable
hours and in a reasonable manner;

Sec. BB.12 - Construction and ODeration of Taminn Facilities. Unless otherwise ordered or approved
by the Agency, each tanning facility shall be constructed, operated, and maintained to meet the following
minimum requirements:

a. Physical Facilities.

i. The following warning sign shall be posted in the immediate proximity (within 1 meter) .of
each piece of tanning equipment; it shall be readily legible, clearly visible, and not _
obstructed by anybarrier, equipment, or other item present so that the user can easily view .
the warning sign before enerwg the ultraviolet light generating equipment: .’

.F&LURE TO USE PROTECTIVE EYEWEAR MAY RESULT
IN SEVEREBURNS 0RLONGrTERM’INJUR.Y TO TlXE EYES..

Medications or cosmetics may increase your sensitivity to the ultmviolet-
tidiation Consult a physician before using sunlamp if you tie
.,using medications or have a history of skin problems or believe
yourselfespecially sonkitive to sunlight.

If you do not tan in the sun, you are unlikely to tan from the use of this
product.

The iettering on each warning sign shall be at least 10~millimeters high for all words shown
in capital letters and at least 5 millimeters high for all lower case letters.

ii. Only tanning equipment manufactured and certified to comply with 21 CFk Part 1040,
Section 1040.20, “Sunlamp products and ultr&olet lamps intended for use in sunlamp
products,” shall be used in tanning facilities- Compliance shall be based on the standard in
effect at the time of manufacture. as shown on the device identification label required by 21
CFR Part 1010, Section 1010.3.
.

SSRCR Vbhme If - October 1996 Sec. BB. 12
.. .
111, Each tanning equipment shall have a timer which comphes with the requirements of 21
CFR Part 1040, Section 1040.20(c)(2). The maximum timer intewal shah not exceed the
manufacturer’s maximum recommended exposure time. No timer interval shall have an
error greater than 10% of the maximum timer interval for the product.

V. There shall be physical barriers to protect consumers from injury induced by touching or
breaking the lamps.,

vi. Addition$requirements
: ‘. ; .,for stand-up
-: booths: _
.
(1) There shah be physical barriers or other means such as handrails or floor’markings
to indicate the proper exposure distance between ultraviolet Iamps and the . ..
consumer’s skin; .. . .
- ._
(2) 7 The ~~nkuction of the booth sh&be.such that-it willtit&and the stress of use .’
and the inipact of a falling person;

ii. Prior to initial exposure each consumer shah be provided the opportunity to read a copy of
the warning specified in BB. 12a.i. The operator shah then request that the consumer sign
a statement that the information has been read and understood. For illiterate or visually
handicapped persons, the warning statement shall be read by the operator in the presence
of a witness. Both the witness and the operator shall sign the statement.

BB6
.

I

See. BB.12 - BB.13 SRCR Volume N - October 1996

...
111. A record shall be kept by the facility operator of each consumer’s total number of tanning
visits and tanning times.

iv. A written report of any tanning injury shall be forwarded to the Agency within 5 working
days of its occurrence or knowledge thereof The report shall include:

(1) The name of the affected individual;

(2) The name and location of the tanning facility involved,

(3) The nature of the injury;

(4) Name and,address of health care provider, if any;

(5) Any other information considered relevant to the situation.

V. No minor shall be allowed to use the tanning facilityunless the minor provides a consent.
form signed by the parent or legalguardian. The parent or guardianshall have been
provided with the basic information required under BB.12a.i.

vi. Defective or burned-out lamps or filters shall be replaced with a type intended for use in
that de&e as specified on the product Iabel on the tanning equipment, or, ;Uith lamps or
filters that are “equivalent” under the Food and Drug Adsninistration regulat$ons and
policies applicable at the time of lamp marw&cture.

vii. Each operator must be adequately-trained, Proof of training must be maintained in the
facility and available for inspection: Training shall include:

(1) ‘The requirements of these regulations;

(2) Procedures for correct operation of the facility;

(3) Recognition of injury or overexposure;

(41 Manufacturer’s procedures for operation and maintenance of tanning equipment;

(5) Emergency procedures in case of injury.
. ..
VW. A list of operators trained in accordance with BB. 12c.v& shall be maintained and available
at the facility.

Sec. BB.14 - Severabilitv. If any provision, clause, section, sentence or paragraph of these regulations
or the application thereofto any person shalt be held to be invalid, such invalidity shall not affect the

BB7
SRCR lfolunte If - October 1996
SCC- 8B. I4 - BB. 1j
remaining provisi,oris or applications ofthe regulations. The.valid part of any provision, clause section
sentence or paragraph shall be given independence Corn the invalid provisions or applications, kd to &is I
end these regulations are hereby declared to be severable.

Sec. BB.15 - Efkctive Date. [here insert relevant efkcti+e date.]

.

.T . .

.

:
. .
. .
.; .
. .
,:

_’

/ ‘. .
: :. : .. :

, . . ‘. .-
1

:
. . .

” .a,
. :

_

.

.

BB8
1996 Ratimale for Parf BB

.

1996
RATXONALE

PART RR
REGULATIONS FOR TANNING FAClLlTlES

Introduction
The use of ultraviolet tanning equipment for cosmeticpurposeshasbeen a growing industry for a number of years,
to the point where several million citizens, young and old, receivetanning sessionseach year.
Concern over the health eEects of ultraviolet eqosure to these sources has caused the Food and Drug ’
&hub&ration to promulgate a performancestandardfor sunlamp products; which%e&me effective May 7,198O.
This performance standard is cl&fly a man&Xuring standard
While there is still.au active home purchase market for ultmvioket tar&g machines, a sizable commercial’
tanning industry has also grown up. This market is not.confined to commerciaStanning salons alone. Rather,
units can be found in, beauty parlors, health clubs, apartment complexes,nail shops, sesorts,bars, etc.
Training of operators, instructions to clients, even time of exposureis left entirely to the.whim of the unit owner or
employee. This includes the crucial instructions on eye protection.
The Food and Drug Administration, the American Dermatology Association, and the U.S. Surgeon General’s
Office are but a few groups that recognize the hazard of ultraviolet tanning and support its control and regulations.
Part BR is qxrcemed with the issuanceof license/regis;ration authoriziag.the exposure of the general population to
artificial ultraviolet tanning sources,i.e., tanning beds,stand-up booths, and facial units.
This Part is needed to provide specific standardsand performance objectivesfor facilities offering nonmedical or
unintentionai exposure to ultravioIet radiation to the publi< in other words, Mlities’ofl&iug cosmetic exposure.
These objectives include recordkeeping, equipment performance, safety p&ting, training of operators; and
knowledgeable consent of the user.
Currently only .Foodand Drug Administration regulations are available and only cover manufacturing ‘standards of
commercial tanning equipment, and as such do not concern themselveswith numerous safety aspectsof the units
once in the field, or how the licenseecomplies with those standa&